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Biomedical subjects

S A Dahanukar

Publications and source records attributed to S A Dahanukar.

At least 19 recordsLinked to original sources

Adaptogenic properties of six rasayana herbs used in Ayurvedic medicine.

Plants from all over the world such as Eleutherococcus senticosus, Panax ginseng, Raponticum carthamoides, Rhodiola rosea, Withania somnifera and Ocimum sanctum have been extensively evaluated for their adaptogenic potential. However, none of them has been successfully introduced as an adaptogen in the clinic. This paper discusses some of the problems in evaluation of adaptogens which have precluded their inclusion as clinically useful drugs. We further discuss our results with six rasayana plants from Ayurveda, which were studied for their adaptogenic potential. The whole, aqueous, standardized extracts of selected plants (Tinospora cordifolia, Asparagus racemosus, Emblica officinalis, Withania somnifera, Piper longum and Terminalia chebula) were administered orally to experimental animals, in a dose extrapolated from the human dose, following which they were exposed to a variety of biological, physical and chemical stressors. These plants were found to offer protection against these stressors, as judged by using markers of stress responses and objective parameters for stress manifestations. Using a model of cisplatin induced alterations in gastrointestinal motility, the ability of these plants to exert a normalizing effect, irrespective of direction of pathological change was tested. All the plants reversed the effects of cisplatin on gastric emptying, while Tinospora cordifolia and Asparagus racemosus also normalized cisplatin induced intestinal hypermotility. Tinospora cordifolia was also tested for its ability to modulate the changes occurring in the phagocytic activity of peritoneal macrophages after exposure of rats to either carbon tetrachloride or horse serum. It was found to normalize the phagocytic function irrespective to the direction of change, complying to the definition of an adaptogen. All the plant drugs were found to be safe in both acute and subacute toxicity studies. Studies on the mechanisms of action of the plants revealed that they all produced immunostimulation. The protection offered by Tinospora cordifolia against stress induced gastric mucosal damage was lost if macrophage activity was blocked. Emblica officinalis strengthened the defence mechanisms against free radical damage induced during stress. The effect of Emblica officinalis appeared to depend on the ability of target tissues to synthesize prostaglandins. Recent data obtained with Tinospora cordifolia suggest that it may induce genotypic adaptation, further opening the arena for more research and experimentation.

Adaptation, Physiological↗

Effect of prazosin GITS, atenolol, nifedipine SR, and enalapril on ADP-induced platelet aggregation.

A randomized, observer-blind, parallel-group study was carried out to compare the effect of prazosin GITS, atenolol, nifedipine SR, and enalapril on platelet aggregation, measured at a time expected to coincide with trough plasma levels of these drugs. 24 patients (age-30 to 60 yrs) with uncomplicated mild to moderate hypertension who completed a placebo run-in phase successfully were recruited in this study. They were randomly allocated to one of the 4 treatments: prazosin GITS 2.5 mg OD (Group 1), atenolol 50 mg OD (Group II), nifedipine SR 20 mg BD (Group III), and enalapril 5 mg OD (Group IV). All the drugs were given for 7 days, and blood samples were collected at 0 hr on day 1 (pre-treatment) and day 8 (post-treatment). Based on the dose (incremental concentrations of ADP)--response (% maximum aggregation) curve obtained, 2.5 microM/L of ADP was used to compare % inhibition of platelet aggregation among the 4 groups. We found that prazosin GITS inhibited % maximum aggregation significantly (p = 0.02) at 2.5 microM/L of ADP. Such inhibitory effect was not seen in any of the other groups. The inhibition produced by prazosin GITS differed significantly from the action of the other 3 drugs (p < 0.05). This antiplatelet effect of prazosin GITS bears more clinical relevance in view of the fact that it was seen at a time which is expected to coincide with the trough plasma levels of prazosin.

Adenosine Diphosphate↗

Leech therapy for complicated varicose veins.

Several methods of limb bandaging have been described to reduce the oedema and enhance ulcer healing in complicated varicose veins, with varying success rates. Leech therapy has never before been tried for the same. We evaluated the effectiveness of medicinal leech therapy in producing venous decongestion, reversal of oedema, hyperpigmentation and healing of varicose ulcer(s). Whether the leech selectively sucks venous blood was also investigated. Hirudo medicinalis (medicinal leech) was applied to the area surrounding the varicose ulcer(s) in 20 patients with varicose veins with complications and the patients monitored for ulcer healing, and decrease in hyperpigmentation, oedema and limb girth. The partial pressure of O2 (pO2) of 7 patients' arterial and venous blood was compared to that sucked by the leech. After leech therapy all the ulcers showed healing, while 95 per cent of patients showed a decrease in oedema and limb girth. Seventy five per cent patients demonstrated a decrease in hyperpigmentation. The mean pO2 of blood sucked by the leech was 40.05 +/- 7.24 mmHg, which was similar to the mean pO2 of the patients' venous blood (34.33 +/- 8.4 mmHg). Thus it appears from this study that the medicinal leech sucks venous blood and aids ulcer healing, and can probably therefore be used as an effective adjunct in the management of complicated varicose veins. This however requires further evaluation by controlled trials.

Adolescent↗

Cardiac surgery and plasma digoxin levels.

Cardiopulmonary bypass (CPB) can induce several haemodynamic alterations and therefore influence pharmacokinetics of various drugs. In order to assess the effect of CPB on plasma digoxin levels, these were monitored in patients undergoing open heart surgery involving CPB (n = 11), over a 24 hour period, starting just prior to commencement of surgery. For comparison, plasma digoxin was also monitored in a group of patients (n = 10) who underwent cardiac surgery not involving CPB. In 7 of the 11 patients in the CPB group, plasma digoxin levels (ng/ml) were significantly (p < 0.01) lower at the end of 24 hours (0.654 +/- 0.094) than basal levels (1.3114 +/- 0.2498). In contrast, in the non CPB group, 7 of 10 patients showed significantly higher (p < 0.001) plasma levels (ng/ml) at the end of 24 hours (0.477 +/- 0.125) as compared to basal levels (0.26 +/- 0.098). Thus, rather than the type of surgery, it appears that the pre-operative levels of plasma digoxin influence its pharmacokinetics.

Adult↗

Emblica officinalis: a novel therapy for acute pancreatitis--an experimental study.

Acute necrotising pancreatitis is associated with an unacceptably high mortality for which no satisfactory remedy exists. Emblica officinalis (E.o.) is a plant prescribed in Ayurveda, the Indian traditional system of medicine, for pancreas-related disorders. This study was carried out to evaluate the protective effect of E.o. against acute necrotising pancreatitis in dogs. Pancreatitis was induced by injecting a mixture of trypsin, bile and blood into the duodenal opening of the pancreatic duct. Twenty eight dogs were divided into 4 groups (n = 6-8 each): GpI--control, GpII--acute pancreatitis, GpIII--sham-operated, GpIV--pretreatment with 28 mg E.o./kg/day for 15 days before inducing pancreatitis. Serum amylase increased from 541.99 +/- 129.13 IU/ml to 1592.63 +/- 327.83 IU (p <0.02) 2 hrs after the induction of pancreatitis in GpII. The rise in serum amylase in both GpIII and GpIV was not significant. On light microscopic examination, acinar cell damage was less and the total inflammatory score was significantly lower in the E.o. treated group as compared to GpII. Electron microscopy confirmed this and showed an increased amount of smooth endoplasmic reticulum and small, condensed granules embedded in a vacuole. More studies are needed to explore the clinical potential of E.o. and its mechanism of action.

Acute Disease↗

Can we do away with PTBD?

Percutaneous Transhepatic Biliary Drainage (PTBD) is performed in surgical jaundice to decompress the biliary tree and improve hepatic functions. However, the risk of sepsis is high in these patients due to immunosuppression and surgical outcome remains poor. This raises a question--can we do away with PTBD? To answer this query a study was carried out in 4 groups of patients bearing in mind the high incidence of sepsis and our earlier studies, which have demonstrated immunotherapeutic potential of Tinospora cordifolia (TC): (A) those undergoing surgery without PTBD (n = 14), (B) those undergoing surgery after PTBD (n = 13). The mortality was 57.14% in Group A as compared to 61.54% in Group B. Serial estimations of bilirubin levels carried out during the course of drainage (3 Wks) revealed a gradual and significant decrease from 12.52 +/- 8.3 mg% to 5.85 +/- 3.0 mg%. Antipyrine half-life did not change significantly (18.35 +/- 4.2 hrs compared to basal values 21.96 +/- 3.78 hrs). The phagocytic and intracellular killing (ICK) capacities of PMN remained suppressed (Basal: 22.13 +/- 3.68% phago. and 19.1 +/- 4.49% ICK; Post drainage: 20 +/- 8.48% Phago and 11.15 +/- 3.05% ICK). Thus PTBD did not improve the metabolic capacity of the liver and mortality was higher due to sepsis. Group (C) patients received TC during PTBD (n = 16) and Group (D) patients received TC without PTBD (n = 14). A significant improvement in PMN functions occurred by 3 weeks in both groups (30.29 +/- 4.68% phago, 30 +/- 4.84% ICK in Group C and 30.4 +/- 2.99% phago, 27.15 +/- 6.19% ICK in Group D). The mortality in Groups C and D was 25% and 14.2% respectively during the preoperative period. There was no mortality after surgery. It appears from this study that host defenses as reflected by PMN functions play an important role in influencing prognosis. Further decompression of the biliary tree by PTBD seems unwarranted.

Adolescent↗

Inhibition of phagocytes by cyclosporin in vitro.

Cyclosporin is an immunosuppressant that acts by selectively inhibiting the activation of T lymphocytes. Its effects on monocytes and neutrophils are not well explored. We investigated the in vitro effects of cyclosporin on these cells, harvested from venous blood from nine healthy, non-smoking volunteers. In vitro incubation of monocytes with increasing concentrations of cyclosporin (5, 25 and 625 micrograms) depressed their phagocytosis by 22%, 32% and 49%, respectively, compared to the control values. The intracellular killing capacity of monocytes decreased by 26%, 31% and 43% with these doses, and neutrophil phagocytosis was depressed in a similar manner (16%, 30% and 40%). Patients receiving cyclosporin are susceptible to infections, and inhibition of these phagocytic cells by cyclosporin may be partly responsible for this. Neutrophil chemotaxis is reduced in patients with impaired renal function. Treating these patients with cyclosporin may in addition suppress the phagocytic function of these cells.

Cells, Cultured↗

Involvement of prostaglandins in chilli-induced early gastric vascular damage in adult Wistar rat.

OBJECTIVE: To explore the role of prostaglandins in protecting against chilli-induced early gastric vascular damage. METHODS: Early gastric vascular damage was induced in rats by oral administration of 8 mg/Kg chilli extract. The damage was assessed by estimating spectrophotometrically the amount of Evan's blue leaking into gastric tissue and luminal contents 10 min after exposure to chilli. Further groups of rats were pretreated with misoprostol (10, 25 or 50 micrograms/Kg) or dazmegrel (1, 5 or 25 mg) to evaluate their protective effects. RESULTS: Both misoprostol and dazmegrel were able to reduce gastric vascular damage induced by chilli in a dose-dependent fashion. CONCLUSION: Prostaglandins may play a role in protecting against chilli-induced early gastric vascular damage.

Animals↗

Polymorphonuclear and monocyte functions in measles.

The depression of immune responses during measles infection has been recognized since the early 20th century. Acute bacterial infections are the most common cause of morbidity and mortality in measles. This study investigated the phagocytic and bactericidal or fungicidal capacities of polymorphonuclear cells (PMN) and monocytes during measles infections. When 14 children with measles were compared with 25 healthy controls, a significant depression in PMN and monocyte function was found. Of these 14 children, seven developed acute bacterial infections. These seven children were compared with 11 children who had acute bacterial infections without measles. It was found that PMN in patients with measles did not achieve an activated state, as expected with acute infections. Serum immunoglobulins were not altered in these patients. These results confirm previous reports of depressed phagocytic and bactericial capacities of PMN in measles, and further document that peripheral blood monocyte functions are also depressed in measles.

Acute Disease↗

Antipyrine clearance: prognostic marker for obstructive jaundice.

A prospective study was undertaken to determine prognostic markers for patients with obstructive jaundice. Along with routine liver function tests, antipyrine clearance was determined in 20 patients. Four patients died after basal investigations. Five patients underwent definitive surgery. The remaining 11 patients were subjected to percutaneous transhepatic biliary decompression. Four patients died during the drainage period, while surgery was carried out for seven patients within 1-3 weeks of drainage. Of 20 patients, only six patients survived. Basal liver function tests were comparable in survivors and nonsurvivors. Discriminant analysis of the basal data revealed that plasma bilirubin, proteins and antipyrine half-life taken together had a strong association with mortality. A mathematical equation was derived using these variables and a score was computed for each patient. It was observed that a score value greater than or equal to 0.84 indicated survival. Omission of antipyrine half-life from the data, however, resulted in prediction of false security in 55% of patients. This study highlights the importance of addition of antipyrine elimination test to the routine liver function tests for precise identification of high risk patients.

Adult↗

Immunotherapeutic modulation of intraperitoneal adhesions by Asparagus racemosus.

The hypothesis that macrophages appear to play a pivotal role in the development of intraperitoneal adhesions and that modulation of macrophage activity, therefore, is likely to provide a tool for prevention of adhesions, was tested in the present study. Effect of Asparagus racemosus, an indigenous agent with immunostimulant properties, was evaluated in an animal model of intraperitoneal adhesions induced by caecal rubbing. Animals were sacrificed 15 days following surgery. The peritoneal macrophages were collected to assess their activity. At the same time, peritoneal cavity was examined for the presence of adhesions, which were graded. A significant decrease was observed in the adhesion scores attained by animals receiving Asparagus racemosus. This was associated with significant increase in the activity of macrophages (70.1 +/- 2.52), compared to that in surgical controls (53.77 +/- 10.8). These findings support our hypothesis and provide a novel approach for the prevention and management of post-operative adhesions.

Adjuvants, Immunologic↗

Modulation of immunosuppression in obstructive jaundice by Tinospora cordifolia.

A clinical study was undertaken to determine the immune status of patients with obstructive jaundice. Screening of 16 patients for phagocytic and microbicidal activity of polymorphonuclear cells (PMN) revealed a significant depression (21.2 +/- 3.7% phagocytosis and 20.85 +/- 4.5% intracellular killing) of these functions, as compared to normal values (30.37 +/- 5.1% and 26.41 +/- 4.3% respectively). An animal model of cholestasis was also established, using rats, in which a significant depression of activity of PMN and peritoneal macrophages was observed. These cellular abnormalities were found to precede and predispose to infection. The rats also showed an increased susceptibility to Escherichia coli infection (mortality rate 77.78%). A defect was detected in their serum responsible for depressing the function of phagocytic cells. An attempt was made to improve this immunosuppression by treating the rats with water extract of T. cordifolia 100 mg/kg for 7 days, following development of cholestasis. The extract improved the cellular immune functions. Mortality rate following Esch. coli infection was significantly reduced to 16.67 per cent. This study showed that cholestasis results in immunosuppression and therefore indicates the need for an immunomodulator in management of obstructive jaundice. The plant T. cordifolia seems to meet this need by consolidating host defence mechanism.

Adult↗

Comparative study of immunomodulating activity of Indian medicinal plants, lithium carbonate and glucan.

The protective effects of Asparagus racemosus (AR) and Tinospora cordifolia (TC) against myelosuppression induced by single doses of cyclophosphamide (CP) have been previously reported. Presented here are the results of a comparative study between AR, TC, glucan and lithium carbonate against the myelosuppressive effects of single and multiple doses of cyclophosphamide in mice. Cyclophosphamide was administered as a single dose 200 mg/kg subcutaneously to one group of mice, while a second group received 3 doses of 30 mg/kg intraperitoneally. Both groups received AR, TC and lithium orally for 15 days before CP. Glucan was administered intravenously in 3 doses, before cyclophosphamide in the first group and together with cyclophosphamide in the second group. In both groups peripheral and differential WBC counts were done before and after drug treatment and serially after cyclophosphamide injection. All four drugs produced leucocytosis with neutrophilia. When compared to control group, all 4 drugs prevented, to varying degrees, leucopenia produced by cyclophosphamide. We conclude, therefore, that both indigenous plants, AR and TC, are potent immunostimulants, with effects comparable to lithium and glucan. They need further evaluation in patients receiving cytotoxic drugs.

Adjuvants, Immunologic↗