Random Allocation

Conditional cash transfer (CCT) programs link public transfers to human capital investment in the hopes of alleviating current poverty and reducing its intergenerational transmission. Whereas nearly all studies of their effects have focused on youth, CCT programs may also have an impact on aging adults by increasing household resources or inducing changes in allocations of time of household members, which may be of substantial interest, particularly given the rapid aging of most populations. This article contributes to this underresearched area by examining health and work impacts on the aging for the best-known and most influential of these programs, the Mexican PROGRESA/Oportunidades program. For a number of health indicators, the program appears to significantly improve health, with larger effects for recipients with a greater time receiving benefits from the program. Most of these health effects are concentrated on women.

Social status impacts reproductive behavior in diverse vertebrate species, but little is known about how it affects brain morphology. We explore this in the naked mole-rat, a species with the most rigidly organized reproductive hierarchy among mammals. Naked mole-rats live in large, subterranean colonies where breeding is restricted to a single female and small number of males. All other members of the colony, known as subordinates, are reproductively suppressed. Subordinates can become breeders if removed from the colony and placed with an opposite sex partner, but in nature most individuals never attain reproductive status. We examined the brains of breeding and subordinate naked mole-rats of both sexes, including several regions linked to reproduction and shown to be sexually dimorphic in other mammals. Stereological analyses revealed that neural morphology depends on status, such that breeders, regardless of sex, had more cells than subordinates in the ventromedial nucleus of th...

Learning the association between one stimulus (a condition stimulus, CS) and another (unconditioned stimulus, US) can be impaired by prior exposure to the CS alone-latent inhibition (LI). Current theories attempting to elucidate the cognitive deficit in schizophrenia have used the abolition of LI in schizophrenia as an indicator of attentional dysfunction. However, it has always been unclear if human and animal LI are measuring the same psychological processes. It is obviously important to clarify this relationship so that theoretical and experimental developments in the rat do not mislead the investigation of brain-behaviour relationships in schizophrenia. LI in the rat is strongly dependent upon context. Our aim was to examine the context specificity of LI in humans and specifically to: (1) investigate whether participants' belief that they are in a different context is sufficient to abolish LI, even though there is no physical change in the environment; (2) produce a context manipulation that is immune to alternative interpretation in terms of stimulus generalization decrement; and (3) investigate whether a "tonic" change of context reduces or abolishes human LI, thus complementing previous reports using a "phasic" change of context. In two experiments we manipulated context in either the real world or a virtual world, and showed that LI is abolished by a change of context in adult humans.

OBJECTIVES: This study estimates the quantity and geographic distribution of discarded needles on the streets of Baltimore, Md, during the 2 years after a needle exchange program opened. METHODS: Thirty-two city blocks were randomly sampled. Counts were taken of the number of syringes, drug vials, and bottles before the needle exchange program opened and then at 6 periodic intervals for 2 years after the program opened. Nonparametric and generalized estimating equation models were used to examine change over time. RESULTS: Two years after the needle exchange program opened, there was a significant decline in the overall quantity of discarded needles relative to that of drug vials and bottles (background trash). The block mean of number of needles per 100 trash items was 2.42 before the program opened and 1.30 2 years later (mean within-block change = -0.028, P < .05). There was no difference in the number of discarded needles by distance from the program site. CONCLUSIONS: These ...

Manganese (Mn) is an essential element and it acts as a cofactor for a number of enzymatic reactions, including those involved in amino acid, lipid, protein and carbohydrate metabolism. Excessive exposure to Mn can lead to poisoning, characterized by psychiatric disturbances and an extrapyramidal disorder. Mn-induced neuronal degeneration is associated with alterations in amino acids metabolism. In the present study, we analyzed whole rat brain amino acid content subsequent to 4 or 8 intraperitoneal (ip) injections, with 25 mg MnCl 2 /kg/day, at 48-hour (h) intervals. We noted a significant increase in glycine brain levels after 4 or 8 Mn injections (p<0.05 and p<0.01, respectively) and arginine also after 4 or 8 injections (p<0.001). Significant increases were also noted in brain proline (p<0.01), cysteine (p<0.05), phenylalanine (p<0.01) and tyrosine (p<0.01) levels after 8 Mn injections vs. the control group. These findings suggest that Mninduced alterations in amino acid levels secondary to Mn affect the neurochemical milieu. neurotoxicity; brain; manganese; γ-aminobutyric acid (GABA); glutamate; amino acids Classically, Mn neurotoxicity is characterized by deregulation of glutamatergic , γaminobutyric acid (GABAergic) and dopaminergic (DAergic) systems. Amino acids are not only indispensable for protein synthesis, but also play important

Evaluations of the nutritional effect of antibiotics have largely centered on effects related to the digestibility and utilization of protein and energy. The current study evaluated the potential effect of virginiamycin (VIR) on P digestibility in swine. A total of 70 barrows (mean initial BW = 51 to 64 kg) were used in 4 nutrient-balance experiments. A basal, corn-soybean meal diet that was not supplemented with any inorganic source of P was used in each experiment. In Exp. 1, two diets were tested: basal vs. basal plus 11 mg/kg of VIR. In Exp. 2, four diets were used with a 2 × 2 factorial arrangement of 0 and 11 mg/kg of VIR and 0 and 750 phytase (PHY) units/kg of diet (PU/kg). Experiments 3 and 4 were the same as Exp. 2, except PHY was reduced to 300 PU/kg. For all experiments, VIR improved P digestibility (32.71 to 37.72%, P < 0.001) and Ca digestibility (54.99 to 58.30%, P = 0.002). The addition of PHY improved both P and Ca digestibility (P < 0.001); 750 PU/kg increased P digestibility 27.3% (from 34.6 to 61.9%, P < 0.001), whereas 300 PU increased it 13.8% (from 33.4 to 47.2%, P < 0.001). In an experiment conducted to evaluate the long-term effects of VIR on gut microbial profile, pigs (24 gilts and 8

The aim of this trial was to study the influence of choice feeding and cereal type (corn or triticale) during the finishing period on performance of ducks. In total, 624 one-day-old male mule ducks (Cairina moschata × Anas platyrhynchos) were divided into 3 groups differing in the diet they received between 56 and 84 d of age: a commercial complete pelleted diet (control group; AMEn 12.1 MJ/kg, CP 15%), or corn whole seeds (AMEn 14.4 MJ/kg, CP 7.3%) and protein-rich pellets (AMEn 9.9 MJ/kg, CP 22.7%) in 2 separated feeders [choice feeding with corn (CFC) group]; or triticale whole seeds (AMEn 13.0 MJ/kg, CP 10.5%) and protein-rich pellets (AMEn 11.2 MJ/kg, CP 19.5%) in 2 separated feeders [choice feeding with triticale (CFT) group]. From 85 to 96 d, 96 birds/group were overfed with corn. Feed intake (complete pellets or cereal and protein-rich pellets) per pen was measured at 60, 62, 65, 69, 78, and 84 d of age. Body weight and body traits were measured at 56 to 84 d of age. Over th...

The aim of this trial was to study the influence of feed form on the performance, gizzard development and carcass traits of growing geese. Between 42 and 98 days of age, 360 geese (type Maxipalm®) were fed a diet containing 500 g sorghum/kg (nitrogen-corrected apparent metabolizable energy 12.6 MJ/kg, 15.1 g/kg CP). Birds were divided into three groups differing in feed form: complete pellets (Control group,n= 120); a coarse-ground meal (CG group,n= 120); or a mixture containing protein-rich pellets and sorghum whole grains (M group,n= 120). Feed intake per pen (40 birds/pen) was measured weekly between 42 and 98 days of age, and individual live weight (LW) was measured every 2 weeks. At 84 and 98 days of age, 12 birds were slaughtered in each group to measure the gizzard development and body traits. Irrespective of the goose sex, LW at 98 days was lower for the CG group than for the Control group (5555v. 5888 g,P&lt; 0.05 for males and 5039v. 5215 g,P&lt; 0.05 for females). The fee...

The correlation between intratesticular pressure during torsion/detorsion and subsequent testicular function and viability has been reported in several recent studies. We assessed the impact of tunica albuginea incision with tunica vaginalis flap coverage on intratesticular pressure and future histopathological parameters in a rat testicular torsion model. Materials and Methods: A total of 21 rats were divided into 3 groups. Group 1 consisted of 7 controls undergoing a sham operation, group 2 consisted of 7 animals undergoing torsion-detorsion, and group 3 consisted of 7 animals undergoing testicular torsion-detorsion followed by tunica albuginea incision and tunica vaginalis flap coverage. Torsion was created by 720-degree counterclockwise rotation of the left testis for 2 hours. By using a compartment monitor, the intratesticular pressure of the torsed testes was measured before torsion (pretorsion), immediately before torsion repair (pre-detorsion), 5 minutes after detorsion (post-detorsion), and after tunical incision and tunica vaginalis flap application. The correlations between intratesticular pressure values and testicular weight, modified Johnsen score and mean seminiferous tubule diameter were evaluated 4 weeks postoperatively. Results: Median pre-detorsion intratesticular pressure was significantly decreased after detorsion in group 2 (21 vs 7 mm Hg, p Ͻ0.001) and group 3 (23 vs 7 mm Hg, p ϭ 0.001). In addition, median intratesticular pressure after tunica albuginea incision and tunica vaginalis flap coverage in group 3 was significantly less compared to median post-detorsion intratesticular pressure in group 2 (5 vs 7 mm Hg, p ϭ 0.025). Overall no significant difference was detected between groups 2 and 3 regarding median modified Johnsen score, mean seminiferous tubule diameter or median testicular weight. The significant reduction of intratesticular pressure in group 3 did not correlate with testicular weight (r ϭ 0.500, p ϭ 0.391), modified Johnsen score (r ϭ Ϫ0.205, p ϭ 0.741) or mean seminiferous tubule diameter (r ϭ Ϫ0.200, p ϭ 0.747). Conclusions: Tunica albuginea decompression with tunica vaginalis flap coverage is an effective technique for decreasing intratesticular pressure in torsed testes. However, this technique failed to alter the injury of prolonged arterial occlusion in testicular torsion.

The aim of this study was to measure the effect of estradiol-17β (E2) injection on follicle-stimulating hormone (FSH) secretion and egg-laying performance of Japanese quail. Female Japanese quail were housed in cages and fed ad libitum. After a 7-day adaptation period, the birds were randomly assigned to three groups, that is, one control group and two test groups. The birds were weighed, before every injection. The control group was subcutaneously injected with 0.2 ml sesame oil-ethanol mixture, whereas test groups were injected, twice in a week, with 0.2 ml sesame oil-ethanol mixture containing 0.1 or 0.2 mg E2 along the study. One day after the first injection, egg number, egg weight, eggshell strength and food conception were daily recorded. On the last day of the experiment, the birds were injected and 3 h later seven birds from each group were randomly selected for bleeding. Blood samples (2 ml/bird) were collected from the jugular vein for the measurements of serum concentrat...

Phosgene is a chemical widely used in the plastics industry and has been used in warfare. It produces a life-threatening pulmonary edema within hours of exposure, to which no specific antidote exists. This study aims to examine the pathophysiological changes seen with low tidal volume ventilation (protective ventilation (PV)) strategies compared to conventional ventilation (CV), in a model of phosgene-induced acute lung injury. Anesthetized pigs were instrumented and exposed to phosgene (concentration ϫ time (Ct), 2,350 mg ⅐ min ⅐ m Ϫ3 ) and then ventilated with intermittent positive pressure ventilation (tidal volume (TV) ϭ 10 ml ⅐ kg Ϫ1 ; positive end expiratory pressure, 3 cm H 2 O; frequency, 20 breaths ⅐ min Ϫ1 ; fractional concentration of inspired oxygen, 0.24), monitored for 6 hours after exposure, and then randomized into treatment groups: CV, PV (A) or (B) (TV, 8 or 6 ml ⅐ kg Ϫ1 ; positive end expiratory pressure, 8 cm H 2 O; frequency, 20 or 25 breaths ⅐ min Ϫ1 ; fractional concentration of inspired oxygen, 0.4). Pathophysiological parameters were measured for up to 24 hours. The results show that PV resulted in improved oxygenation, decreased shunt fraction, and mortality, with all animals surviving to 24 hours compared to only three of the CV animals. Microscopy confirmed reduced hemorrhage, neutrophilic infiltration, and intra-alveolar edema.

Phosgene is a chemical widely used in the plastics industry and has been used in warfare. It produces a life-threatening pulmonary edema within hours of exposure, to which no specific antidote exists. This study aims to examine the pathophysiological changes seen with low tidal volume ventilation (protective ventilation (PV)) strategies compared to conventional ventilation (CV), in a model of phosgene-induced acute lung injury. Anesthetized pigs were instrumented and exposed to phosgene (concentration ϫ time (Ct), 2,350 mg ⅐ min ⅐ m Ϫ3 ) and then ventilated with intermittent positive pressure ventilation (tidal volume (TV) ϭ 10 ml ⅐ kg Ϫ1 ; positive end expiratory pressure, 3 cm H 2 O; frequency, 20 breaths ⅐ min Ϫ1 ; fractional concentration of inspired oxygen, 0.24), monitored for 6 hours after exposure, and then randomized into treatment groups: CV, PV (A) or (B) (TV, 8 or 6 ml ⅐ kg Ϫ1 ; positive end expiratory pressure, 8 cm H 2 O; frequency, 20 or 25 breaths ⅐ min Ϫ1 ; fractional concentration of inspired oxygen, 0.4). Pathophysiological parameters were measured for up to 24 hours. The results show that PV resulted in improved oxygenation, decreased shunt fraction, and mortality, with all animals surviving to 24 hours compared to only three of the CV animals. Microscopy confirmed reduced hemorrhage, neutrophilic infiltration, and intra-alveolar edema.

The present study was conducted to assess the effect of Pioglitazone, an oral antidiabetic drug with selective PPAR-gamma agonist effect; in a dose of 4 mg/kg B.W. once a day orally for eight weeks on the liver of streptozotocin-induced diabetic rats. Sixty male adult albino Wistar rats were equally randomly into six groups (n=10). Group I: normal control group was received no medication. Group II: distilled water control group, they are non diabetic group and received distilled water once a day orally by gastric tube for 8 weeks. Group III: citrate buffer control group, they are non diabetic received a single intraperitoneal injection of an equivalent amount of vehicle (citrate buffer, pH 4.5) 1 ml/kg at the time of induction. Group IV: Pioglitazone control group, they are non diabetic received pioglitazone HCl, single dose of 4 mg/kg b.w. once a day orally by gastric tube for eight weeks. Group V: diabetic control group, they are streptozotocin-induced diabetic rats that received ...

A population based survey on the prevalence of major blinding disorders was conducted in the Wenchi district in central Ghana between March and May 1991. In 10 villages, 1425 people of 30 years and older were screened, using the WHO eye examination record. The prevalence of bilateral blindness above 30 years proved to be 1.7% (best acuity <3/60): the prevalence oflow vision above 30 years was 20/0% (best visual acuity 6/18 to 3/60). The causes of blindness were determined as cataract (62.5%), onchocerciasis (12.5%), corneal opacity (non-trachomatous) (8.2%), refraction anomalies (4.2%), phthisis bulbi (4.2%), optic atrophy (4.2%), and vascular retinopathy (4.2%). In the Wenchi district, 1-0% of the population over the age of 30 years was found to need a cataract extraction because of blindness of both eyes. Another potential 1-0% needs a cataract extraction because of low vision. A minor second study (n=149) was undertaken in the same district, but in a village in an area near the Black Volta river in which onchocerciasis is endemic. The prevalence of blindness (8.1%) and low vision (3.4%) caused by onchocerciasis and cataract both proved to be higher. The survey provided the basis for a preventive and curative eye care programme.

Nimodipine, a calcium entry blocking agent similar in structure to nifedipine but with selective cerebrovascular dilating effects, has potential use in the therapy and prevention of cerebral vasospasm after intracranial hemorrhage. The authors summarize the effects of calcium entry blockers, review the pharmacology of nimodipine, and discuss both the known and possible interactions of oral nimodipine with physical and pharmacological interventions that neuroanesthesiologists employ for patients with cerebral vasospasm during craniotomy for aneurysm clipping. In a series of 26 patients undergoing aneurysm clipping, the authors found that intraoperative blood pressure tended to be reduced by nimodipine. Although the number of patients was limited by the fact that they were enrolled in a multi-center nimodipine aneurysm study and thus had to meet the criteria for that study, it is concluded that prophylaxis of cerebral vasospasm with nimodipine in patients with ruptured intracranial aneurysm results only in a favorable tendency toward lower systemic blood pressure during craniotomy. 9 aneurysm clipping 9 cerebral vasospasm 9 nimodipine 9 blood pressure 9 calcium entry blocker

✓ Nimodipine, a calcium entry blocking agent similar in structure to nifedipine but with selective cerebrovascular dilating effects, has potential use in the therapy and prevention of cerebral vasospasm after intracranial hemorrhage. The authors summarize the effects of calcium entry blockers, review the pharmacology of nimodipine, and discuss both the known and possible interactions of oral nimodipine with physical and pharmacological interventions that neuroanesthesiologists employ for patients with cerebral vasospasm during craniotomy for aneurysm clipping. In a series of 26 patients undergoing aneurysm clipping, the authors found that intraoperative blood pressure tended to be reduced by nimodipine. Although the number of patients was limited by the fact that they were enrolled in a multi-center nimodipine aneurysm study and thus had to meet the criteria for that study, it is concluded that prophylaxis of cerebral vasospasm with nimodipine in patients with ruptured intracranial ...

Purpose-The objective of this study was to determine if an injection of a novel extracellular matrix scaffold and blood composite (EMBC) after anterior cruciate ligament (ACL) injury would have a mitigating effect on post-traumatic osteoarthritis (PTOA) development in rat knees. Methods-Lewis rats underwent unilateral ACL transection and were divided into three groups: 1) no further treatment (ACLT; n = 10), 2) an intraarticular injection of EMBC on day 0 (INJ0; n = 11), and 3) an intra-articular injection of EMBC on day 14 (INJ14; n = 11). Ten animals received capsulotomy only (n = 10, SHAM group). The OARSI histology scoring of the tibial cartilage and micro-CT of the tibial epiphysis were performed after 35 days. The ratio of intact/treated hind limb forces during gait was determined using a variable resistor walkway. Results-The OARSI cartilage degradation sum score and total degeneration width were significantly greater in the ACLT group when compared to the INJ0 (P = 0.031, and P = 0.005) and INJ14 (P =0.022 and P =0.04) group. Weight bearing on the operated limb only decreased significantly in the ACLT group (P = 0.048). In the rat ACL transection model, early or delayed injection of EMBC ameliorated the significant decrease in weight bearing and cartilage degradation seen in knees subjected to

In earlier studi es it was fo und that glutamatergic tTansmi ssion w ithin the nu cleus accumbens septi is invo lv ed in th e performance o f a learned visual shape discrimin ation in pigeo ns. This study examin es what effects several kinds of glutamate and dopamine an tagonists have on the same task. Pigeons were trained with the relevant di scrimin ation, bil aterall y implanted wi th cannul as into th e nucleus a ccumbens and tested after vari ous transmi ss ion bl ockers had been administered intracereb rally. SCH-23390, a Dl dopamin e antagoni st, at the dose used, had no effect, and Spiperone, a D2-dopamine and 5HT2a-serotonin e antagonist, significa ntly decreased th e error repeat trials. CNQX, a non-N MDA glutamate receptor antago nist, and Cycl oleucine, an antago nist of the glycine allosteri c site of N MDA receptors, had no effect. CGS-19755, a selecti ve competitive N MDA antagonist, significa ntly impai red perfOlm ance by signifi cantly decreasing the percen t correct trials mid in creas ing the error repea t trials. CPPG, a IIIIII metabotropic glutamate antagonist, remarkab ly improved perfonn ance. MMPG, a n Ull metabotropi c g lutamate antagonist, at the dose used, did not have any signifi cant effect. Th e preparation empl oyed may be a use ful ani ma l model of perceptu al di sturb ances in schizophrenia.

Financial management is the core of sustainable business growth, especially in situations of limited resources, market uncertainty, and increased operational complexity. Traditional budgeting and financial planning models tend to be unresponsive and stagnant, thereby limiting their effectiveness in maximizing resource deployment and supporting long-term strategic goals. In a bid to overcome these problems, the study presents a Financial Management Optimization Model (FMOM) to enhance its effectiveness in resource allocation and increase its financial sustainability. The suggested financial decision-making framework addresses multi-objective optimization, accounting for return on investment, cost efficiency, liquidity, and risk-adjusted growth. Sensitivity analysis is conducted as a scenario-driven approach, using linear programming to allocate funds dynamically across operational, strategic, and innovation-oriented business units. The model is confirmed using financial data from small-and medium-sized enterprises over several fiscal periods. Empirical evidence shows that the proposed FMOM significantly improves traditional budgeting techniques, resulting in an average 14.8% increase Acta Innovations • 2026• no. 59:291-300• 292 http://www.actainnovations.com/ • ISSN 2300-5599 • © 2026 in resource utilization efficiency, a 12.3% reduction in operational costs, and a 9.6% increase in overall return on investment. Also, under different market conditions, companies with the optimized allocation strategy reported a 18.1% reduction in liquidity risk and a 11.4% increase in long-term financial growth stability. Such findings demonstrate that the offered optimization framework has the potential to achieve a balance between short-term profitability and long-term sustainability. The paper finds that optimal-based financial management offers a strong, scalable, and data-driven decision-support system that helps an organization improve financial performance, reduce risk, and realize sustainable business development in a competitive world.

Purpose: Microsurgical vasovasostomy and vasoepididymostomy remain technically challenging procedures. Refinements in technique have continually improved patency and pregnancy rates for the 2 procedures in experienced hands. Advances in surgical robotics produced the Da Vinci robot (Intuitive Surgical, Inc., Sunnyvale, California) with motion reduction and no tremor, features that may improve outcomes in microsurgery. We report a randomized prospective study of vasoepididymostomy and vasovasostomy using the Da Vinci robot in rats. Materials and Methods: A total of 24 adult male Wistar rats underwent vasectomy through a midline abdominal incision. Two weeks later the animals were randomized to microsurgical multilayer vasovasostomy, longitudinal vasoepididymostomy or robotic vasovasostomy and vasoepididymostomy groups. Outcomes measured included surgical time, complications, patency and sperm granuloma formation at 9 weeks. Results: Animals were sacrificed 9 weeks after microsurgery. There were no significant differences in complications among the groups. Robotic vasovasostomy was significantly faster than the conventional microsurgical technique (68.5 vs 102.5 minutes, p ϭ 0.002). The robotic and microsurgical vasoepididymostomy groups did not differ significantly in time. Patency rates were 100% for the robotic vasovasostomy and vasoepididymostomy groups, and 90% in the microsurgical vasovasostomy and vasoepididymostomy groups. These differences were not significant. Sperm granulomas were found in 70% of microsurgical vasovasostomy anastomoses and 27% of robotic vasovasostomy anastomoses (p ϭ 0.001). No significant difference in the sperm granuloma rate was found between the robotic or microsurgical vasoepididymostomy groups (42% and 50%, respectively, p ϭ 0.37). Conclusions: To our knowledge we report the first randomized prospective study using the Da Vinci robot for microsurgery. We believe that the improved stability and motion reduction during microsurgical suturing with the robot helped achieve excellent patency rates for vasovasostomy and vasoepididymostomy. The robot may also allow experienced microsurgeons to perform microsurgical procedures in patients at remote locations where no experienced microsurgeons are available.

Objective: To detect and determine disease severity of osteoarthritis (OA) using a probe activated by matrix metalloproteinase-13 (MMP-13) in vivo in the murine destabilised medial meniscus (DMM) surgical model of OA. Design: We have previously described MMP12ap and MMP13ap, internally quenched fluorescent peptide substrate probes that are activated respectively by MMP-12 and MMP-13. Here we used these probes to follow enzyme activity in vivo in mice knees 4, 6 and 8 weeks following DMM surgery. After in vivo optical imaging, disease severity was determined through traditional histological analysis. The amount of probe activation was analysed for discrimination between DMM, contralateral and sham operated knees, as well as for congruence between activity and histological damage. Results: There was no specific activation of MMP12ap at the time points observed between sham operated and DMM operated, or their respective contralateral joints. The activation of the MMP13ap in the DMM model was highest 6 weeks after surgery, but was only specific compared against sham surgery 8 weeks after surgery (1.5-fold increase). The activation of MMP13ap correlated with histological damage 6 and 8 weeks after surgery, with correlations of 0.484 (P ¼ 0.0032) and 0.478 respectively (P ¼ 0.0049). This correlation dropped to 0.218 (P ¼ 0.011) if all data were considered. The current MMP-13 activity probe is suitable for the discrimination between DMM and sham or contralateral knees 8 weeks after surgery, when cartilage loss is typified by the appearance of small fissures up to the tidemark, but not earlier. This activity correlates with the histological damage observed.

Objective: To detect and determine disease severity of osteoarthritis (OA) using a probe activated by matrix metalloproteinase-13 (MMP-13) in vivo in the murine destabilised medial meniscus (DMM) surgical model of OA. Design: We have previously described MMP12ap and MMP13ap, internally quenched fluorescent peptide substrate probes that are activated respectively by MMP-12 and MMP-13. Here we used these probes to follow enzyme activity in vivo in mice knees 4, 6 and 8 weeks following DMM surgery. After in vivo optical imaging, disease severity was determined through traditional histological analysis. The amount of probe activation was analysed for discrimination between DMM, contralateral and sham operated knees, as well as for congruence between activity and histological damage. Results: There was no specific activation of MMP12ap at the time points observed between sham operated and DMM operated, or their respective contralateral joints. The activation of the MMP13ap in the DMM model was highest 6 weeks after surgery, but was only specific compared against sham surgery 8 weeks after surgery (1.5-fold increase). The activation of MMP13ap correlated with histological damage 6 and 8 weeks after surgery, with correlations of 0.484 (P ¼ 0.0032) and 0.478 respectively (P ¼ 0.0049). This correlation dropped to 0.218 (P ¼ 0.011) if all data were considered. The current MMP-13 activity probe is suitable for the discrimination between DMM and sham or contralateral knees 8 weeks after surgery, when cartilage loss is typified by the appearance of small fissures up to the tidemark, but not earlier. This activity correlates with the histological damage observed.

Findings are reported from a study of respite services in which an experimental design was used to assess the impact of respite on families caring for elderly persons. Almost one-third of the 189 families eligible for respite services offered through Medicare waivers failed to use any services. The majority of families chose respite services in their home for frequent periods of 3 hours. Families spent, on average, only 63 percent of their allotted funds. Respite services appeared to delay nursing home placement among families with adult children as caregivers but encouraged placement when spouses were the primary caregivers.

1. In 6 incubation trials a total of 9883 eggs (Ross 308) were incubated from d 1 to 17 under normal incubation conditions (37Á2-37Á4 C) and then sorted into three hatch incubators (control: 37Á2-37Á4 C; chronic warm incubation: 38Á2-38Á4 C, 24 h daily; short-term warm stimulation: 38Á2-38Á4 C, 2 h daily) in incubation trials 1 and 2 or two hatch incubators (control and short-term warm stimulation) in trials 3-6. 2. The one-day-old chicks were selected by sex and chick quality was analysed in random samples using the Pasgarß score. A total of 120 male and 120 female one-day-old chickens from each incubator were used for a 35-d fattening period. 3. Neither chronic nor short-term increase in incubation temperature had a negative effect on hatchability and chick quality. Short-term warm stimulation improved hatchability by more than 1Á5% and was associated with a significantly higher proportion of hatched male chicks. 4. In the subsequent broiler growth trial, the mean daily weight gain of the short-term warm stimulated male broiler chicks was significant higher than for the control group, which results in a body weight increase of 2Á9%. 5. Feed conversion (feed:gain ratio) of the short-term warm stimulated male and female broilers was significantly lower than in the males and females of the control and chronic warm incubated groups. 6. In conclusion, an incubation temperature profile which includes short-term temperature variation can be important in improving poultry performance (European patent pending since March 2008).

Purpose: To identify the surgical trainee benefits through the use of video assisted training (VAT). Methods: Twelve cases of uncomplicated laparoscopic cholecystectomy (LC) were selected. Edited video segments focused on essential intra-operative anatomical structure identification and critical surgical steps. Evaluation of these videos was constructed on a scoring system based on pre and post-teach tests. The mean value of the pre-teach score was 33.2 ± 18.0 points and in the post-teach test the mean value was 66.7 ± 9.7 points. A statistically significant difference was seen when comparing pre and post-teach results (p<.00001). The widespread and the systematic use of video assisted learning may be a useful and economic tool in adjunct to the surgical training techniques practiced until now throughout the surgical community.

All plants have a potential medicinal significance. Medicinal plants are considered as important therapeutic aid for alleviating ailment of humankind. Numerous herbal plants or botanical medicines and polyherbal formulations are used for the treatment of liver diseases (Hepatoprotective). A number of herbal preparations are available in the market. Liver is a vital organ play a major role in metabolism and excretion of xenobiotics from the body. Liver cell injury caused by a range of toxic chemicals (certain chemotherapeutic agents, antibiotic , carbon tetrachloride (CCL 4), paracetamol (PCM), thioacetamide (TAA) etc.), excessive alcohol consumption and microbes is well-studied. The present review is aimed at compiling data on promising phytochemicals from medicinal plants that have been tested in hepatotoxicity models using modern scientific system.

There is controversy concerning the ability of antioxidant vitamins to reduce myocardial infarct size. We sought to determine whether a brief prophylactic treatment of vitamin C or vitamin C plus Trolox (a water-soluble form of vitamin E) could reduce myocardial infarct size in an experimental model. We used an anesthetized open-chest rabbit model in which a branch of the circumflex coronary artery was ligated for 30 minutes followed by 4 hours of reperfusion. Experiments were performed in a randomized and blinded fashion. An IV injection of normal saline pH balanced to 7.4 (control group n = 15), vitamin C (150 mg/kg, n = 14), or vitamin C plus Trolox (150 mg/kg plus 100 mg/kg, respectively, n = 15) was administered prior to coronary occlusion. Collateral blood flow during coronary occlusion was measured by radioactive microspheres, myocardial risk zone (AR) was assessed by blue dye injection, and myocardial infarct size (AN) was assessed by triphenyltetrazolium chloride staining. All rabbits received comparable ischemic insult: Collateral blood flow and AR were similar among all three groups. Infarct size, measured as a percent of AR, did not differ significantly among the controls (21%), vitamin C (29%), or the vitamin C plus Trolox (18%) groups. Therefore, in this ischemia/reperfusion model, antioxidant vitamins did not alter myocardial infarct size.

OBJECTIVE: Systemic PaO2 oscillations occur during cyclic recruitment and derecruitment of atelectasis in acute respiratory failure and might harm brain tissue integrity. DESIGN: Controlled animal study. SETTING: University research laboratory. SUBJECTS: Adult anesthetized pigs. INTER-VENTIONS: Pigs were randomized to a control group (anesthesia and extracorporeal circulation for 20 hr with constant PaO2, n = 10) or an oscillation group (anesthesia and extracorporeal circulation for 20 hr with artificial PaO2 oscillations [3 cycles min¹], n = 10). Five additional animals served as native group (n = 5). MEASUREMENTS AND MAIN RESULTS: Outcome following exposure to artificial PaO2 oscillations compared with constant PaO2 levels was measured using 1) immunohistochemistry, 2) real-time polymerase chain reaction for inflammatory markers, 3) receptor autoradiography, and 4) transcriptome analysis in the hippocampus. Our study shows that PaO2 oscillations are transmitted to brain tissue as detected by novel ultrarapid oxygen sensing technology. PaO2 oscillations cause significant decrease in NISSL-stained neurons (p < 0.05) and induce inflammation (p < 0.05) in the hippocampus and a shift of the balance of hippocampal neurotransmitter receptor densities toward inhibition (p < 0.05). A pathway analysis suggests that cerebral immune and acute-phase response may play a role in mediating PaO2 oscillation-induced brain injury. CONCLUSIONS: Artificial PaO2 oscillations cause mild brain injury mediated by inflammatory pathways. Although artificial PaO2 oscillations and endogenous PaO2 oscillations in lung-diseased patients have different origins, it is likely that they share the same noxious effect on the brain. Therefore, PaO2 oscillations might represent a newly detected pathway potentially contributing to the crosstalk between acute lung and remote brain injury.

PURPOSE: Determine the effects of the MSG (monosodium glutamate) in the offspring of pregnant rats through the comparison of the weight, NAL (nasal-anal length) and IL (Index of Lee) at birth and with 21 days of life. METHODS: Pregnant Wistar rats and their offspring were divided into 3 groups: GC, G10 and G20. Each of the groups received 0%, 10% and 20% of MSG, respectively from coupling until the end of the weaning period. RESULTS: Neither weight nor NAL were different among the groups at birth. The group G20 at birth had an IL lower than the group GC (p&lt;0,05) and with 21 days of life presented weight and NAL lower than the groups G10 and this lower than the GC (p&lt;0,01). Otherwise the G20 at 21 days of life had the IL similar to the other two groups. The weight profit percentage from birth to the 21st day of life was lower in the G20 regarding the other two groups (p&lt;0,01). The G20 had a NAL increase percentage from birth to the 21st day of life lower than the G10 and thi...

Focal segmental glomerulosclerosis (FSGS) is a common histological lesion in adults worldwide. It results from initial podocyte injury, followed by a maladaptive activation of glomerular parietal epithelial cells (PECs), which leads to progressive scarring of glomeruli. Abnormal PEC phenotype is also a hallmark of crescentic glomerulonephritides, another class of severe kidney diseases that complicate small vessel vasculitides. Current knowledge of the pathophysiological mechanisms leading to PEC activation is limited. Recent evidence indicates an active and destructive role for PECs in extra-capillary glomerular diseases. Therefore, targeting such maladaptive responses could represent a novel therapeutic option to prevent kidney failure in patients. Yet, druggable pathways to prevent or stop the pathogenic behavior of PECs are still elusive. Methods: Here, we examined the role of the mineralocorticoid receptor signaling in PECs in two mouse models of glomerular disease involving PEC activation: a robust model of maladaptive FSGS with deoxycorticosterone acetate (DOCA)-salt administration with uninephrectomy, and nephrotoxic serum-induced crescentic glomerulonephritis. We demonstrate that targeting the mineralocorticoid receptor (MR) (Nr3c2) gene specifically in PECs prevents migration and proliferation after DOCA-salt administration with uninephrectomy. Remarkably, both MR deficiency in PECs and mineralocorticoid receptor pharmacological blockade using eplerenone were also effective in preventing extracapillary lesions and glomerular failure in nephrotoxic serum-induced crescentic glomerulonephritis. Additionally, we revealed a significant overlap between pathways triggered by heparin-binding EGF-like growth factor and its receptor signaling and MR signaling. This promoted the migration, proliferation, and epithelial-to-mesenchymal transition of PECs. Conclusions: Together, our results highlight the common role of MR signaling in the pathophysiology of extra-capillary glomerulopathies, FSGS, and crescentic glomerulonephritis. This supports the use of MR antagonists as potential complementary therapeutic agents with original modes of action for severe diseases.

Two experiments were conducted to investigate the effect of i.v. administration of Lcarnitine on selected metabolites in sheep and to determine the feasibility of using L-carnitine to ameliorate the deleterious effects of hyperammonemia in sheep. In Exp. 1, i.v. L-carnitine solutions were administered at three levels in a replicated Latin square: 0 (CONT), 6.36 (CAR 1), and 12.72 (CAR 2 ) mmol L-carnitine/kg .75 BW using Suffolk ewes ( n = 6; average BW 75 ± 3 kg). Plasma L-carnitine concentration was increased ( P < .05) by treatment (51.9 vs 102.3, and 96.4 mmol/L in CONT, CAR 1, and CAR 2, respectively). Plasma glucose concentration was elevated ( P < .05) in CAR 2 and CAR 1. Plasma NEFA concentration was highest ( P < .05) in CAR 2. Area under the response curve for glucose was greater ( P < .02) in CAR 2. In Exp. 2, Suffolk ewes ( n = 16; average BW 48 ± 2 kg) were used in a randomized complete block design with a 2 × 2 factorial treatment arrangement to determine the effects of i.v. Lcarnitine administration during an oral urea load test (OULT). L-Carnitine ( 0 and 6.36 mmol/kg .75 BW) was administered i.v. at 30 min, and an oral urea drench (50% wt/vol; 0 and 300 mg/kg BW) was administered at 60 min. Plasma L-carnitine was increased ( P < .0001) by i.v. L-carnitine. Plasma ammonia N was highest ( P < .0001) in the UREA treatment compared with the CONT, CARN, and CARN + UREA treatments (148 vs 95, 101, and 108 mmol/L, respectively). Intravenous L-carnitine administration influenced plasma glucose and NEFA concentrations in sheep and, when administered 30 min preceding an OULT, prevented the development of subclinical hyperammonemia in sheep.

Sepsis and endotoxaemia occur frequently in biliary obstruction. Impaired Kupffer cell endocytosis is implicated in these events. Tumour necrosis factor and interleukin 6, secreted by Kupffer cells, are important mediators of sepsis. Kupffer cell clearance of endotoxin and secretion of cytokines in experimental obstructive jaundice were investigated. Methods: Wistar rats were randomized to bile duct ligation, sham operation or control. Groups (n = 8) were studied 1 and 3 weeks after operation. Kupffer cell function was assessed using in situ hepatic perfusion. Results: Clearance of endotoxin was signi®cantly depressed 1 week (median (interquartile range) 20á3 (10á5±27á1) per cent) and 3 weeks (22á1 (20á2±23á2) per cent) after bile duct ligation compared with that in respective sham animals (35á5 (29á9±41á6) and 40á9 (37á7±47á0) per cent) and controls (39á5 (37á3±46á8) per cent). Secretion of tumour necrosis factor was signi®cantly greater 1 week (1113á7 (706á5± 1436á8) pg/ml) and 3 weeks (1118á2 (775á7±1484á1) pg/ml) following bile duct ligation compared with that in respective sham animals (114á3 (0±178á5) and 107á6 (63á7±166á4) pg/ml) and controls (0 (0± 20á7) pg/ml). Interleukin 6 was not secreted by sham or control animals but was present in the perfusate from jaundiced animals at 1 and 3 weeks (52á5 (9á9±89á5) and 66á2 (60á2±193á1) pg/ml). Conclusion: These data demonstrate simultaneous impairment of Kupffer cell clearance of endotoxin and increased secretion of proin¯ammatory cytokines in experimental obstructive jaundice. These diverse responses may contribute to the development of sepsis-related complications in biliary obstruction.

Two independently developed patient outcome mea- surement instruments were administered to forty-eight subjects with rheumatoid arthritis using a random cross-over design. The independent estimates of physical disability and pain are highly correlated. Each instrument displayed highly significant relationships with global health, providing evidence for convergent validity. The results demonstrate that health status is composed of at least three major dimensions: physical disability, psychological disability, and pain. (Am J Public Health 1984; 74:159-161.) The chronic diseases affect the quality of life as well as the duration of life, and thus require for their assessment the ability to measure health status effectively.'-9 Two indepen- dent instruments have recently been,'°0" developed to as- sess patient outcome in arthritis and other chronic diseases the Health Assessment Questionnaire (HAQ), and the Ar- thritis Impact Measurement Scales (AIMS); both are self- administered. This study compares these instruments in a randomized crossover study, demonstrates convergent va- lidity for the health status concept, and identifies major components of patient outcome. The HAQ disability and pain instruments consist of 21 questions grouped into nine components graded in an ordinal fashion from 0 to 3.* The AIMS instrument is composed of 49 items. The initial 45 items are summed into nine scales. Each scale is indexed from zero to ten (minimum to maxi- mum disability).** The content of the two instruments overlaps by about 65 per cent. In all cases, however, the actual questionnaire items are different. Both instruments contain a single horizontal visual analog scale assessing the patient's perception of arthritis status, providing a "global health estimate." *(I) dressing and grooming; (2) arising; (3) eating; (4) walking; (5) reach; (6) personal hygiene; (7) gripping and grasp; (8) activities; (9) pain. **(l) mobility; (2) physical activity; (3) activities of daily living (ADL); (4) dexterity; (5) household activities; (6) pain; (7) social activity; (8) depression; (9) anxiety.

Objective—To determine whether solar load distribution pattern on a solid nondeformable ground surface is the product of contact erosion and is the mirror image of load distribution on a deformable surface in horses. Animals—30 clinically normal horses. Procedures—Solar load distribution was compared among 25 clinically normal horses during quasistatic loading on a solid nondeformable surface and on a highly deformable surface. Changes in solar load distribution patterns were evaluated in 5 previously pasture- maintained horses housed on a flat nondeformable surface. Changes in solar load distribution created by traditional trimming and shoeing were recorded. Results—Unshod untrimmed horses had a 4-point (12/25, 48%) or a 3-point (13/25, 52%) wall load distribution pattern on a flat solid surface. Load distribution on a deformable ground surface was principally solar and located transversely across the central region of the foot. Ground surface contact areas on solid (24.2 ± 8.62 cm...

Background. Several clinical studies have demonstrated a general superiority of biphasic waveform defibrillation compared with monophasic waveform defibrillation using epicardial lead systems. To test the breadth of utility of biphasic waveforms in humans, a prospective, randomized evaluation of defibrillation efficacy of monophasic and single capacitor biphasic waveform pulses was performed for two distinct nonthoracotomy lead systems as well as for an epicardial electrode system in 51 cardiac arrest survivors undergoing automatic defibrillator implantation. Methods and Results. The configurations tested consisted of a right ventricular-left ventricular (RV-LV) epicardial patch-patch system, an RV catheter-chest patch (CP) nonthoracotomy system, and a coronary sinus (CS) catheter-RV catheter nonthoracotomy system. For each configuration, the defibrillation current and voltage waveforms were recorded via a digital oscilloscope to measure defibrillation threshold voltage, current, resistance, and stored energy. Biphasic waveform defibrillation proved more efficient than monophasic waveform defibrillation for the epicardial RV-LV system (4.8 ±4.1 versus 6.7+ 4.9 J, p=0.047) and the nonthora- cotomy RV-CP system (23.4+ 11.1 versus 34.3± 10.4 J, p=0.0042). Biphasic waveform defibril- lation thresholds were not significantly lower than monophasic waveform defibrillation thresholds for the CS-RV nonthoracotomy system (15.6±7.2 versus 20.0±11.5 J, p=0.11). Biphasic waveform defibrillation proved more efficacious than monophasic waveform defibril- lation in 13 of 20 patients (65%) with RV-LV epicardial patches, 10 of 15 patients (67%) with an RV-CP nonthoracotomy system, and nine of 16 patients (56%) with an RV-CS nonthora- cotomy system. Conclusions. Biphasic pulsing was useful with nonthoracotomy lead systems as well as with epicardial lead systems. However, the degree of biphasic waveform defibrillation superiority appeared to be electrode system dependent. Furthermore, for a few individuals, biphasic waveform defibrillation proved less efficient than monophasic waveform defibrillation, regard- less of the lead system used. (Circulation 1991;84:665-671) N onthoracotomy defibrillation in humans has proven to require higher energy levels than epicardial defibrillation.1'2 Any tool that makes defibrillation with a nonthoracotomy lead sys- tem easier will improve the likelihood that open-chest surgery can be avoided when implantable defibrilla- From the Divisions of Cardiology and Cardiothoracic Surgery, Departments of Medicine (G.

The central Ending of the study by Bruneau et al. (1) is the existence of a statistical association between attendance at needle exchange programs (NEPs) and higher HIV incidence in injection drug users (IDUs). This association cannot be removed by addition to the multivariate models of potential confounding variables relating to differences in risk behaviors relevant to HTV infection in NEP attenders versus nonattenders. The assumption then made is that the potential causal link is operating in the direction NEP =£> HTV incidence, and thus the conclusion is drawn that NEP attendance must somehow increase the risk of becoming infected with HTV. As pointed out by Lurie (2), an alternative explanation is that the NEP attenders, in specific contexts that may vary from city to city, have a higher risk of HTV infection in comparison with nonattenders, before they ever attend NEPs. This is suggested by the data of Bruneau et al. ( ), in that both the frequency of risk behaviors relevant to HTV infection and the prevalence of HTV infection were higher in NEP users than in non-NEP users at study enrollment. Furthermore, this possibility has been directly demonstrated in a recent paper by Hahn et al. (3), in which HTV incidence in IDUs who subsequently used or did not use NEPs was measured before NEP attendance. The HIV incidence before NEP attendance was indeed higher in the group that subsequently became NEP attenders than in those who did not (relative risk = 24.6 for HIV seroconversion in NEP users vs. nonusers). Thus, while this paper shows the same type of statistical association between NEP use and HIV incidence as that by Bruneau et al. (1), the difference is that, since Hahn et al. (3) have pre-NEP use incidence data, it is possible to assume that the potential causal link is, in fact, operating in the HIV =$> NEP direction, i.e., the direction opposite to that postulated by Bruneau et al. (1). As the authors state, "The high seroconversion rate among future exchangers reflects a self-selection of high-risk users into the exchanges, not an effect of exchange itself (3, p. 162). The Montreal data (1), as stated by Lurie (2), do indeed show that NEP users are at higher risk of HTV infection than are non-NEP users. Unfortunately, however, in the absence of data on HTV incidence prior to NEP attendance, Bruneau et al. ( ) are nevertheless forced to explain this observation in terms of what NEPs might be doing to cause a higher HTV incidence. However, risk behaviors in this context (of an observational study not designed to directly evaluate NEPs, such as this study) are merely a proxy for HIV incidence, and it cannot be assumed that any questionnaire, however complete and well-designed, could ever collect information pertaining to every single, possible, relevant risk behavior. It is, furthermore, becoming increasingly apparent that to comprehend drug-use interactions and their potential effects on HTV incidence amongst IDUs, ethnographic and sociologic studies are clearly required in addition to quantitative epidemiologic data (4, 5). Thus, while we do not wish to underestimate the importance of, for example, the study of HIV incidence rate t Time

To characterize the pharmacokinetic and pharmacodynamic profiles of the recombinant human erythropoietin (rhEPO)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres in rats. Methods: The rhEPO-loaded microspheres were prepared using a solid-in-oil-in-water emulsion method. Pharmacokinetics and pharmacodynamics of the rhEPO-loaded microspheres were evaluated in male Sprague-Dawley rats. The serum rhEPO level was determined with ELISA. The level of anti-rhEPO antibody in the serum was measured to assess the immunogenicity of rhEPO released from the microspheres. Results: rhEPO was almost completely released from the PLGA microspheres in vitro, following zero-order release kinetics over approximately 30 d. After intramuscular injection (10 000 or 30 000 IU rhEPO/kg) in the rats, the serum rhEPO concentration reached maximum levels on d 1, then decreased gradually and was maintained at nearly steady levels for approximately 4 weeks. Furthermore, the release of rhEPO from the PLGA microspheres was found to be controlled mainly by a dissolution/diffusion mechanism. A good linear correlation (R 2 =0.98) was obtained between the in vitro and in vivo release data. A single intramuscular injection of the rhEPOloaded PLGA microspheres (10 000 or 30 000 IU rhEPO/kg) in the rats resulted in elevated hemoglobin and red blood cell concentrations for more than 28 d. Moreover, the immunogenicity of rhEPO released from the PLGA microspheres was comparable with that of the unencapsulated rhEPO. The results prove the feasibility of using the PLGA-based microspheres to deliver rhEPO for approximately 1 month.

Background: Oxygen is an essential substance for wound healing. Limited studies have shown that topical oxygen can influence healing. This study evaluated the effects of a topical oxygen emulsion (TOE) on burn wound healing. Methods: A porcine second-degree burn wound model was used in the study. Burn wounds were randomly assigned to TOE, vehicle control, and no-treatment (air) groups. Effects of TOE on the granulation formation and angiogenesis were studied using Hematoxylin & Eosin histological analysis. Protein production and gene expression of types I and III collagen and vascular endothelial growth factor (VEGF) were determined using immunofluorescent staining and Reverse Transcription and Polymerase Chain Reaction (RT-PCR), respectively. The TOE treated wounds exhibited better angiogenesis and granulation tissue formation by histology examination. The immunofluorescence staining and RT-PCR analysis demonstrated that protein production and mRNA expression of VEGF and collagen III were significantly higher in TOE treatment group than vehicle alone and air control groups, while there was no significant difference in the level of collagen I. Our data demonstrates that TOE enhances burn wound healing via stimulating the expression of VEGF and type III collagen and strongly indicates the potential use of TOE in wounds.

Recent models of causation place the concept of CAUSE within a broader framework of concepts that includes the notions of LETTING, HINDERING, HELPING and PREVENTING. In each model, the related concepts are defined in terms of a small set of conceptual distinctions. This paper examines the relationship between the cognitive and linguistic systems. Specifically, we investigate whether these models of causation can capture the distinctions that underlie the semantics of causal verbs. There are a number of structures that can be used to express the notion of CAUSE in English and other languages, including causal connectives (e.g., because), prepositions (because of, thanks to) and lexical causatives, i.e., verbs that encode both the notions of CAUSE and RESULT, as in Peter broke the stick (i.e., caused the stick to break). Yet another means of expressing CAUSE is the use of a verb that includes the notion of CAUSE without specification of a particular RESULT, as in the verbs cause, let, help or prevent

Emerging evidence supports an important role for T cells in the genesis of hypertension. Because this work has predominantly been performed in experimental animals, we sought to determine whether human T cells are activated in hypertension. We used a humanized mouse model in which the murine immune system is replaced by the human immune system. Angiotensin II increased systolic pressure to 162 versus 116 mm Hg for sham-treated animals. Flow cytometry of thoracic lymph nodes, thoracic aorta, and kidney revealed increased infiltration of human leukocytes (CD45(+)) and T lymphocytes (CD3(+) and CD4(+)) in response to angiotensin II infusion. Interestingly, there was also an increase in the memory T cells (CD3(+)/CD45RO(+)) in the aortas and lymph nodes. Prevention of hypertension using hydralazine and hydrochlorothiazide prevented the accumulation of T cells in these tissues. Studies of isolated human T cells and monocytes indicated that angiotensin II had no direct effect on cytokine ...

Angiotensin II-induced hypertension is associated with an increase in T-cell production of interleukin-17A (IL-17A). Recently, we reported that IL-17A(-/-) mice exhibit blunted hypertension, preserved natriuresis in response to a saline challenge, and decreased renal sodium hydrogen exchanger 3 expression after 2 weeks of angiotensin II infusion compared with wild-type mice. In the current study, we performed renal transporter profiling in mice deficient in IL-17A or the related isoform, IL-17F, after 4 weeks of Ang II infusion, the time when the blood pressure reduction in IL-17A(-/-) mice is most prominent. Deficiency of IL-17A abolished the activation of distal tubule transporters, specifically the sodium-chloride cotransporter and the epithelial sodium channel and protected mice from glomerular and tubular injury. In human proximal tubule (HK-2) cells, IL-17A increased sodium hydrogen exchanger 3 expression through a serum and glucocorticoid-regulated kinase 1-dependent pathway....

Rationale: Inflammation and adaptive immunity play a crucial role in the development of hypertension. Angiotensin II and probably other hypertensive stimuli activate the central nervous system and promote T-cell activation and end-organ damage in peripheral tissues. Objective: To determine if renal sympathetic nerves mediate renal inflammation and T-cell activation in hypertension. Methods and Results: Bilateral renal denervation using phenol application to the renal arteries reduced renal norepinephrine levels and blunted angiotensin II–induced hypertension. Bilateral renal denervation also reduced inflammation, as reflected by decreased accumulation of total leukocytes, T cells, and both CD4 + and CD8 + T cells in the kidney. This was associated with a marked reduction in renal fibrosis, albuminuria, and nephrinuria. Unilateral renal denervation, which partly attenuated blood pressure, only reduced inflammation in the denervated kidney, suggesting that this effect is pressure inde...