Improvement in baroreflex control of renal sympathetic nerve activity in obese Sprague Dawley rats following immunosuppression.

AIM: This investigation explored the hypothesis that in obesity an inflammatory response in the kidney contributed to a renal nerve-dependent blunting of the baroreflex regulation of renal sympathetic nerve activity. METHODS: Rats received a normal (12% kcal) or high-fat (45% kcal) diet for 8 weeks plus daily injections of vehicle (0.9% NaCl i.p) or tacrolimus (0.25 mg kg-1 day-1 i.p) from weeks 3-8. Following anaesthesia, left renal sympathetic nerve activity was recorded, baroreflex gain curves were generated, by infusing phenylephrine and sodium nitroprusside, and cardiopulmonary baroreceptors challenged by infusing a saline load. RESULTS: The high-fat diet elevated weight gain and adiposity index by 89 and 129% (both, P < 0.001). Mean blood pressure (132 ± 4 vs 103 ± 5 mmHg), fractional noradrenaline excretion and creatinine clearance (5.64 ± 0.55 vs 3.32 ± 0.35 mL min-1 kg-1 ) were 28, 77 and 69% higher (all P < 0.05), but urine flow and fractional sodium excretions were 42 and 72% (both P < 0.001) lower compared to normal rats. Plasma and renal TNF-α and IL-6 concentrations were fourfold to fivefold (P < 0.001) and 22 and 20% higher (both, P < 0.05), in obese rats but normalized following tacrolimus. In obese rats, baroreflex sensitivity was reduced by 80% (P < 0.05) but restored by renal denervation or tacrolimus. Volume expansion reduced renal sympathetic nerve activity by 54% (P < 0.001) in normal and obese rats subjected to renal denervation and tacrolimus, but not in obese rats with an intact renal innervation. CONCLUSION: Obesity induced a renal inflammation and pointed to this being both the origin of autonomic dysregulation and a potential focus for targeted therapy.

Enhanced expression of endothelial nitric oxide synthase in the myocardium ameliorates the progression of left ventricular hypertrophy in L-arginine treated Wistar-Kyoto rats.

The present study investigated the role of endothelial nitric oxide synthase (eNOS) enzyme in the development of left ventricular hypertrophy (LVH) in Wistar-Kyoto rats. The effect of L-arginine administration on cardiac structure, arterial stiffness, renal and systemic hemodynamic parameters was studied and the change in expression of eNOS and cystathione γ lyase (CSE) in the myocardium of LVH rats was evaluated. LVH was induced using isoprenaline (5 mg/kg, S.C.) and caffeine (62 mg/L in drinking water) for 14 days. Following to that, L-arginine (1.25 g/L in drinking water) was given for 5 weeks as a donor of NO. eNOS and CSE gene expressions were down regulated in the LVH group by about 35% and 67% respectively when compared to control. However, in the LVH group treated with L-arginine there was up regulation of eNOS by almost 27% and down regulation in CSE by 24% when compared to control (all P < 0.05). Heart index and H2S plasma levels were reduced by almost 53% in the L-arginine treated LVH group compared to the control (all P < 0.05). Mean arterial pressure, heart rate and pulse wave velocity were reduced while renal blood perfusion increased in L-arginine treated LVH rats compared to their untreated counterparts (all P < 0.05). The enhanced expression of eNOS in L-arginine treated LVH rats resulted in the amelioration of oxidative and haemodynamic parameters suggesting that NO system is an important therapeutic target in cardiac and LV hypertrophies.

Obesity depresses baroreflex control of renal sympathetic nerve activity and heart rate in Sprague Dawley rats: role of the renal innervation.

AIM: This study investigated the role of the renal innervation in arterial and cardiopulmonary baroreflex regulation of renal sympathetic nerve activity (RSNA) and heart rate (HR) in rats fed a high-fat diet to induce obesity. METHODS: Rats received either a normal (12% kcal) or high (45% kcal) fat diet for 60 days. On day 61, rats were anesthetized and prepared for recording left RSNA. In one group, the renal nerves remained intact, while in the other, both kidneys were denervated. Baroreflex gain curves for RSNA and HR were generated by increasing and decreasing blood pressure. Low-pressure baroreceptors were challenged by infusing a saline load. RESULTS: Mean blood pressure was 135 mmHg in the fat-fed and 105 mmHg (P < 0.05) in normal rats. Weight gain, adiposity index and creatinine clearance were 37, 82 and 55% higher (P < 0.05-0.001), but urine flow rate and fractional sodium excretions were 53 and 65% (both P < 0.001) lower, respectively, in the fat-fed compared to normal rats. In fat-fed rats with innervated kidneys, RSNA and HR arterial baroreflex sensitivities were reduced by 73 and 72% (both P < 0.05) but were normal in renally denervated rats. Volume expansion decreased RSNA by 66% (P < 0.001) in normal rats, but not in the intact fat-fed rats and by 51% (P < 0.01) in renally denervated fat-fed rats. CONCLUSION: Feeding a high-fat diet caused hypertension associated with dysregulation of the arterial and cardiopulmonary baroreflexes which was dependent on an intact renal innervation. This suggests that in obese states neural signals arising from the kidney contribute to a deranged autonomic control.

Renal denervation restores the baroreflex control of renal sympathetic nerve activity and heart rate in Wistar-Kyoto rats with cisplatin-induced renal failure.

AIM: There is evidence that in chronic renal failure, the sympathetic nervous system is activated. This study investigated the role of the renal innervation in suppressing high- and low-pressure baroreflex control of renal sympathetic nerve activity and heart rate in cisplatin-induced renal failure. METHODS: Renal failure was induced using cisplatin (5 mg kg(-1) , i.p.) and the rats used 7 days later. Groups of rats were anaesthetized and prepared for measurement of renal sympathetic nerve activity and heart rate. Acute unilateral or bilateral renal denervation was performed, and renal sympathetic nerve activity and heart rate baroreflex gain curves were generated while the cardiopulmonary receptors were stimulated using an acute saline volume load. RESULTS: Cisplatin administration reduced (P < 0.05) glomerular filtration rate by 27%, increased sodium fractional excretions fourfold, plasma creatinine and kidney index by 39 and 30% respectively, (all P < 0.05) compared with control rats. In the renal failure rats, baroreflex sensitivity for renal sympathetic nerve activity and heart rate was reduced (P < 0.05) by 29% and 27% (both P < 0.05) compared with control animals. Bilateral, but not unilateral, renal denervation restored baroreflex sensitivity to normal values. Volume expansion reduced (P < 0.05) renal sympathetic nerve activity by 34% in control rats, but remained unchanged in the renal failure rats. Unilateral and bilateral renal denervation progressively restored the volume expansion induced renal sympathoinhibition to control values. CONCLUSION: These findings reveal a significant role of the renal sensory innervation in cisplatin-damaged kidneys which blunt the normal baroreflex control of renal sympathetic nerve activity.

Shift work--problems and its impact on female nurses in Udaipur, Rajasthan India.

Abstract : There is good evidence that shift work has negative effects on workers health, safety and performance. It is quite appropriate that attention is paid to this very important feature of socio-technical systems, which may adversely affect mental and physical health, social life and safety of shift workers. Research into the impact of shift work on professionals has consistently identified a range of negative outcomes in physical, psychological, and social domains (Akerstedt, 1988; Costa, Lievore, Casaletti, Gaffuri, & Folkard, 1989; Kogi, 2005; Paley & Tepas, 1994). Hospitals, the biggest employer in the health care field, employ more night shift workers than any other industry. It can therefore be inferred that in medical domain high percentage of workforce may be affected by problems related to shift work. Thus the present study will provide knowledge base for the problems faced by the female nurses. The present study was undertaken with an objective of getting an insight into the problems faced by female nurses in shift work. . It was found that the female nurses in India worked on roaster pattern of change in shift every seven days. They did not have a say in the change of duties, it could only be done on mutual grounds. Partners of younger group did not much adjust to their shift pattern this created stress among the nurses.The results showed that the female nurses in both the age groups i.e. 30-45 years and 45-60 years faced many problems related to health and well being, fatigue, social and domestic situations. They could not give much time to their children in particular. Travelling in nights was risky for them. Common problem was the insufficient sleep during night shifts. The nurses had to cater to the needs of the family, children in particular along with the adjustments to be made due to shift work. They had to sometimes do the night duties and attend social functions as a part of their duty. Children and husband in some cases did not cooperate this lead to frustration. When asked as to whether they would could shift job if they get regular one more than 50 % said yes this means that there need to be come training and intervention for the shift workers and their family so that the problems faced and their impact on personal health of the female nurses could be reduced.

The ayurveda education in India: how well are the graduates exposed to basic clinical skills?

"Ayurveda" is an ancient system of healthcare that is native to India. At present, in India, there are more than 240 colleges that offer a graduate-level degree (Bachelor of Ayurvedic Medicine and Surgery-BAMS) in Ayurveda. Even though the Central Council of Indian Medicine, the governing body that monitors the matters related to Ayurveda education, has imposed various educational norms and regulations, the standard of education has been a cause of concern in recent years. The mushrooming of substandard Ayurvedic colleges is the most important factor that is being held responsible for this kind of erosion in the standards. The present study is a mailed survey, which was carried out to evaluate the "Extent of exposure to basic clinical skills during BAMS course" as perceived by the sample groups of students and teachers drawn from 32 Ayurvedic educational institutions spread all over India. A methodically validated questionnaire was used as the tool in the study, to which 1022 participants responded. The study indicates that there are some serious flaws in the existing system of the graduate-level Ayurveda education. Since the Ayurvedic graduates play an important role in the primary healthcare delivery system of the country, governing bodies are required to take necessary steps to ensure the adequate exposure of the students to basic clinical skills. Along with the strict implementation of all the regulatory norms during the process of recognition of the colleges, introducing some changes in the policy model may also be required to tackle the situation.

Prevention of acetaminophen induced hepatorenal damage in mice with rhizomes of Glycyrrhiza glabra A histophysiological study.

Protective role of Gycyrrhiza glabra rhizomes (roots) at three dose levels (100, 75, & 50 mg/kg/bw) against sublethaldose (300 mg/kg/bw) of acetaminophen (paracetamol) induced hepatorenal damage has been assessed in mice. Parameters of study were glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), billirubin, alkaline phosphatase (ALP) as liver function tests, creatinine and urea as kidney function tests and histology for pathology. G.glabra could antagonize acetaminophen induced both,hepato and nephrotoxicity in dose dependent manner. No protection provided by a single dose of G.glabra (1.5 gm/kg/bw) against lethal dose of acetaminophen (1gm/kg/bw). Probable protective role is discussed.

Global challenges of graduate level Ayurvedic education: A survey.

In the present day scenario, Ayurveda is globally being perceived in several contradictory ways. Poor quality of Ayurveda graduates produced as a result of poorly structured and poorly regulated education system is at least one of the important factors responsible for this scenario. The present study was carried out to evaluate the 'Global challenges of graduate level Ayurvedic education' and is based on the responses of Ayurvedic students and Ayurvedic teachers from various educational institutions of India to a methodically validated questionnaire. As the study indicates, the poor standard of Ayurvedic education in India is definitely a cause of concern. The curriculum of Bachelor of Ayurvedic Medicine and Surgery (BAMS) course of studies is required to be reviewed and restructured. The syllabi are required to be updated with certain relevant topics like laws governing the intellectual property rights, basic procedures of standardization of medicinal products, fundamental methods of evaluating the toxicity of the medicinal products, essentials of healthcare management and the basics of cultivation and marketing of medicinal plants. Furthermore, the study suggests that the Ayurvedic academicians are required to be trained in standard methods of research and documentation skills, and the educational institutions are required to be encouraged to contribute their share in building up the evidence base for Ayurveda in the form of quality education and research.

Interaction between renin-angiotensin and sympathetic nervous systems in a rat model of pressure overload cardiac hypertrophy.

1 A raised cardiac workload activates neurohormones which will increase muscle mass and shift contractility to the right along the Frank-Starling curve. 2 This study examined the interaction between the SNS and RAS in contributing to vascular responsiveness following the development of cardiac hypertrophy due to aortic banding. 3 Sprague Dawley rats (180-200 g) were assigned to one of six groups; Normal, Sham-operated, Aortic Banded (AB), Aortic Banded treated with losartan (ABLOS), Aortic Banded treated with 6-hydroxydopamine (ABSYMP) and Aortic banded treated with both losartan and 6-hydroxydopamine (ABSYMPLOS). A constricting band was placed around the supra renal aorta on day zero with drug treatment from day 37 to day 44. Vasopressor responses to noradrenaline, phenylephrine, methoxamine and angiotensin II were measured on day 45. 4 The magnitudes of the MAP responses to all vasoactive agents, expressed as percentage changes, were similar in Normal and Sham groups, but reduced in the AB group. ABLOS group showed attenuated response to ANGII whereas all responses were enhanced in the ABSYM group. 5 A positive interaction between the two systems was observed with alpha(1A)-adrenoceptors identified as a major component of SNS and AT(1) receptors of RAS to induce vasopressor effects.

Local breeds, livelihoods and livestock keepers' rights in South Asia.

In South Asia, and throughout the developing world, the predominant official approach to livestock development has been improvement of production by means of upgrading local breeds via cross-breeding with exotic animals. This strategy has led to the replacement and dilution of locally adapted breeds with non-native ones. This has resulted in an alarming loss that has been estimated by the Food and Agriculture Organization of the United Nations to amount to one breed every two weeks. Based on selected case studies this paper argues that development strategies using locally adapted breeds and species are much more likely to benefit livestock keepers whilst also maintaining domestic animal diversity and bearing a smaller ecological footprint. It also analyses the rationale for "Livestock Keepers' Rights", a principle that grew out of the struggle of traditional livestock keepers to retain control over their production resources, such as grazing areas and breeding stock, in the face of unfavourable policy environments.

Inhibition of Ang II and renal sympathetic nerve influence dopamine-and isoprenaline-induced renal haemodynamic changes in normal Wistar-Kyoto and spontaneously hypertensive rats.

1. This study was undertaken to elucidate the effects of inhibiting the renin-angiotensin system (RAS) with losartan, and acute unilateral renal denervation on renal haemodynamic responses to intrarenal administration of vasoconstrictor doses of dopamine and vasodilator doses of isoprenaline in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2. Acute unilateral renal denervation of the left kidney in rats was confirmed by a drop in the renal vasoconstrictor response to renal nerve stimulation (P < 0.05) along with diuresis and natriuresis. Rats were pretreated with losartan for 7 days and thereafter animals fasted overnight were anaesthetized (sodium pentobarbitone, 60 mg/kg i.p.) and acute renal haemodynamic responses studied. 3. Dose-response curves were constructed for dopamine and isoprenaline that induced falls or increases in renal blood flow, respectively. It was observed that renal vascular responses were greater in the denervated as compared with rats with intact renal nerves (all P < 0.05). Dopamine-induced renal vasoconstrictor responses were markedly lower in losartan-treated denervated WKY and SHR compared with their untreated counterparts (all P < 0.05). It was also observed that in losartan-treated and denervated WKY rats the vasodilatory responses to isoprenaline were markedly lower compared with untreated rats (all P < 0.05). However, in SHR, under the same conditions, there was no difference in the renal response to isoprenaline whether or not rats were treated with losartan (P > 0.05). 4. The data obtained showed that the renal vasoconstrictor effect of dopamine depends on intact renal nerves and RAS in WKY and SHR. Isoprenaline responses were likewise sensitive to renal denervation and RAS inhibition in WKY rats but not SHRs. Our observations reveal a possible relationship between renal AT(1) receptors and alpha(1)-adrenoceptors in WKY and SHR. There is also evidence to suggest an interaction between renal beta-adrenoceptors and AT(1) receptors in WKY rats.

Hypocholesterolemic effect of Terminalia chebula fruit (Myrobalan) in mice.

Cholesterol fed mice were administered powdered myrobalan, the fruit of Terminalia chebula, to evaluate its antiatherogenic activity. Male mice were fed a diet containing 1% cholesterol with or without myrobalan for 100 days. The cholesterol containing diet fed to mice caused increased food intake, body weight, serum cholesterol, triglyceride, thickening of the walls of aorta and shrinkage in its lumen (group 2) . The oral administration of myrobalan to mice on atherogenic diet successfully reversed these effect (group 3). However, the food intake was observed to be high as compared to the control animals. Control animals (group 1) received only the vehicle. The results suggest that myrobalan has hypocholesterolemic effect in animals fed with atherogenic diet.

Prevention of toxic effects of mercuric chloride on Some male accessory organs in mice with a Multiherbal drug "Speman".

Adult Swiss albino male mice exposed to mercuric chloride via drinking water at 5 µg/ml for 100 days revealed significant reduction in the wet weight and severe histopathological changes in male accessory organs, poor level of serum testosterone and infertility. These effects were reduced remarkable and fertility was restored when drug (12.50 mg/mouse/day orally) was administered during mercury exposure for 100days or after Hg-exposure for next 60 days (Post therapy). Natural recovery after mercury exposure for 60 days remind ineffective. Probable action of herbal drug based on the presence of the active principles of constituents (i.e Orchis mascula, Mucuna pruriens, parmelia perlata, Argyreia speciosa, Tribulus terristris, Leptadenia reticulate, Lactuca scariola and Hygrophila spinosa) is discussed in detail.

Haematological effects of hexachlorocyclohexane (HCH) in mice--results and possibilities.

Adult male Swiss albino mice when exposed to a chlorinated insecticide hexachlorocyclohexane (HCH or BHC) at 100 mg/mouse/ once oral and i.p. both for acute exposures and 500 ppm and 10 ppm in food for 100 and 400 days respectively for intermediate and chronic exposures. Haematological observations revealed HCH-induced anaemia.

Prevention of mercuric chloride induced histopathological changes in the small intestine of mice with LIV-52.

Mercuric chloride was administered in drinking water to mice at 1 mM and 5 mM for 100 and 30 days respectively. Lower concentration caused mild pathological changes in the small intestine while higher concentration caused severe pathological changes. Pathological symptoms were less pronounced when Liv52 was administered along with 5 mM mercuric chloric and Hg-induced changes were totally absent when drug was used along with 1 mM HgCl2 solution. After Hg-exposure at both concentrations mice were allowed to recover naturally or with drug (Post-therapy). Again, use of drug appeared useful. At least under laboratory conditions this herbal drug seems to reduce Hg-induced pathological changes in small intestine of mice.

Studies on removal of malathion from water by means of activated charcoal.

The utility of activated charcoal for the removal of malathion from saline waters has been explored. The adsorption capacity of charcoal for malathion has been found to be 117 mg g-1. Adsorption follows the Freundlich adsorption isotherms, the value of k and 1/n for charcoal being 1.6 and 0.60, respectively. Malathion can be eluted with methanol or ethanolic potassium hydroxide.

Cardiac glycosides. 7. Sugar stereochemistry and cardiac glycoside activity.

Digitoxigenin alpha-L-, beta-L-, alpha-D-, and beta-D-glucosides; alpha-L-, beta-L-, alpha-D-, and beta-D-mannosides; and alpha-L- and beta-L-rhamnosides were stereoselectively synthesized from the corresponding sugar tetrabenzyl trichloroacetimidates. The Na+,K+-ATPase receptor inhibitory activities of these glycosides (as a measure of receptor binding) were compared with those of digitoxigenin, digitoxigenin 6'-hydroxy-beta-D-digitoxoside, digitoxigenin beta-D-galactoside, and digitoxigenin beta-D-digitoxoside. The observed activities reveal that a given sugar substituent may have a role in binding of some glycoside stereoisomers, but not others. With alpha-L- and possibly beta-L-rhamnosides, the 5'-CH3 and 4'-OH appear to have a predominant role in binding to the Na+,K+-ATPase receptor. Addition of a 6'-OH to form the corresponding mannosides dramatically disrupts the effect of both the 5'-CH3 and 4'-OH in prompting receptor binding of the alpha-L isomer. However, with the beta-L isomer, some influence of 4'-OH, 3'-OH, and 2'-OH binding remains. With beta-D-glycosides, binding via the "5'-CH3 site" appears to be of little importance and addition of a 6'-OH diminishes activity only slightly. With these beta-D-glycosides, an equatorial 4'-OH, axial 3'-OH, and equatorial 2'-OH groups appear to contribute to binding.

Cardiac glycosides. 6. Gitoxigenin C16 acetates, formates, methoxycarbonates, and digitoxosides. Synthesis and Na+,K+-ATPase inhibitory activities.

A series of 17 gitoxigenin 16 beta-formates, acetates, and methoxycarbonates was synthesized, including their 3 beta-acetates, formates, and digitoxosides. A 16 beta-formate group was generally found to increase activity 30 times, a 16 beta-acetate group 9-12 times, while a 16 beta-methoxycarbonate decreased activity by two-thirds. 3 beta-Formates and acetates had little effect on activity by themselves, but sometimes reduced the activity-increasing properties of 16 beta-formates and acetates. A 3 beta-digitoxoside increases the activity of gitoxigenin by 15 times, but the effect is less if the 16 beta-group is esterified. And finally, a 16-one decreases activity dramatically. These data suggest an important role for C16 esters and possibly the presence of a separate binding site on Na+,K+-ATPase corresponding to the cardenolide C16 position.

The effect of 16 beta-substitution on the structure and activity of digitoxigenin: is there an additional binding interaction with Na+,K+-ATPase?

We have studied the basis of the effect of 16 beta-substitution on the structure and activity of digitoxigenin derivatives by examining the crystal structures of these compounds and their inhibitory activity toward the receptor for these drugs, Na+,K+-ATPase. To understand the increase in inhibitory activity of the 16 beta-ester compounds and the decrease in activity of gitoxigenin (16 beta-hydroxydigitoxigenin), both with respect to digitoxigenin, we have compared the observed conformations of gitoxigenin, gitoxigenin 16 beta-formate, and other 16 beta-esters to that of digitoxigenin. Our data do not support the possibility of hydrogen bonding between the 16 beta-hydroxyl of gitoxigenin and the lactone ring, previously suggested to account for the decreased activity of gitoxigenin vis à vis digitoxigenin, but, rather, suggest that the decreased activity may be due to an intramolecular hydrogen bond between the hydroxyls on C-14 and C-16 and an unusual D-ring conformation which combine to alter the carbonyl oxygen of the lactone ring away from the putative active position. In contrast, the 16 beta-ester moiety has a preferred conformation which may serve to fix the lactone ring in the active conformation. Thus, the increased activity of the 16 beta-esters cannot be explained by altered carbonyl oxygen position and may be related to an additional receptor binding site for the ester moiety.