Rama Vaidya

Thyroid hormone regulates hippocampal neurogenesis in the adult rat brain

We have examined the influence of thyroid hormone on adult hippocampal neurogenesis, which encompasses the proliferation, survival and differentiation of dentate granule cell progenitors. Using bromodeoxyuridine (BrdU), we demonstrate that adult-onset hypothyroidism significantly decreases hippocampal neurogenesis. This decline is predominantly the consequence of a significant decrease in the survival and neuronal differentiation of BrdU-positive cells. Both the decreased survival and neuronal differentiation of hippocampal progenitors could be rescued by restored euthyroid status. Adult-onset hyperthyroidism did not influence hippocampal neurogenesis, suggesting that the effects of thyroid hormone may be optimally permissive at euthyroid levels. Our in vivo and in vitro results revealed that adult hippocampal progenitors express thyroid receptor isoforms. The in vitro studies demonstrate that adult hippocampal progenitors exhibit enhanced proliferation, survival and glial differentiation in response to thyroid hormone. These results support a role for thyroid hormone in the regulation of adult hippocampal neurogenesis and raise the possibility that altered neurogenesis may contribute to the cognitive and behavioral deficits associated with adult-onset hypothyroidism.

Menopause and metabolic syndrome: A study of 498 urban women from western India

Introduction: Metabolic syndrome (MS) is a cluster of risk factors for future development of type 2 diabetes mellitus and cardiovascular diseases. Menopausal transition with its incidental hormonal changes is considered to contribute to the development of MS. However, age is known to influence MS risk factors. Objective: The present study explores the prevalence of MS in pre- and postmenopausal women from western India. Methods: Four hundred and ninety eight women above 35 years of age, participating in womens health care program were assessed for the prevalence of MS using two criteria- International Diabetes Federation criteria (IDF) and Harmonization (H_MS) criteria. Results: Prevalence of MS amongst postmenopausal women was significantly higher (P < 0.001) than that in premenopausal women by both, IDF (premenopausal 45% and postmenopausal 55%) and H_MS criteria (premenopausal 44% and postmenopausal 56%). However, this significance disappeared when data was adjusted for the confounding variable of age.

Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera) in healthy volunteers

Ashwagandha (Withania somnifera) (WS), a “rasayana” drug, is recommended for balavardhan and mamsavardhan. The study was intended to evaluate dose-related tolerability, safety, and activity of WS formulation in normal individuals. The design was prospective, open-labeled, variable doses in volunteers. Eighteen apparently healthy volunteers (12M:6F, age:18-30 years, and BMI: 19-30) were enrolled. After baseline investigations, they received WS capsules (Rx) (aqueous extract, 8:1) daily in two divided doses with increase in daily dosage every 10 days for 30 days (750 mg/day ×10 days, 1 000 mg/day × 10 days, 1 250 mg/day × 10 days). Volunteers were assessed for symptoms/signs, vital functions, hematological and biochemical organ function tests. Muscle activity was measured by hand grip strength, quadriceps strength, and back extensor force. Exercise tolerance was determined using cycle ergometry. Lean body weight and fat% were computed from skin fold thickness measurement. Adverse events were recorded, as volunteered by the subjects. Repeated measures ANOVA, McNemars test, and paired t test were employed. All but one volunteer tolerated WS without any adverse event. One volunteer showed increased appetite, libido, and hallucinogenic effects with vertigo at the lowest dose and was withdrawn from study. In six subjects, improvement in quality of sleep was found. Organ function tests were in normal range before and after the intervention. Reduction in total- and LDL- cholesterol and increase of strength in muscle activity was significant. Total body fat percentage showed a reduction trend. WS, in escalated dose, was tolerated well. The formulation appeared safe and strengthened muscle activity. In view of its traditional Rasayana use, further studies are planned to evaluate potential of this drug in patients of sarcopenia.

Normalization of visual fields following bromocriptine treatment in hyperprolactinemic patients with visual field constriction

Two patients with galactorrhea-amenorrhea and bilateral visual field defects were studied. Routine radiologic examination of each patient revealed a normal sella turcica and no demineralization of the posterior clinoid process. Serum prolactin levels were elevated (patient V. G., 80 ng/ml; patient S. R., 204 ng/ml). Within 2 months of bromocriptine therapy, the serum prolactin levels were normal (patient V. G., 12.21 ng/ml; patient S. R., 8.25 ng/ml) and the bilateral visual field defects were corrected. Bromocriptine has been shown to control prolactin secretion in patients with prolactin-secreting pituitary tumors. Normalization of restricted visual fields following bromocriptine therapy indicates the possibility of an anatomical regression of pituitary hyperplasia or an underlying prolactin-producing microadenoma. It is speculated that the modality of functional galactorrhea reflects hyperplasia of the lactotrophs preceding a nodular and ultimately an adenomatous change. The continuous and prolonged administration of bromocriptine may prevent such a progressive sequence. Further experience is required to validate this possibility.

Presence of prolactin in human cervical mucus.

The presence of prolactin in human cervical mucus was demonstrated by radioimmunoassay. The levels of prolactin in cervical mucus were significantly higher (260 ng/ml +/- 47.5 SE) than those in sera of normally menstruating women (30.28 ng/ml +/- 2.0 SE).

Plasmodium DNA Fluoresces With Berberine A Novel Approach for Diagnosis of Malarial Parasites

The key to reducing mortality and morbidity associated with malaria is rapid diagnosis and early, effective therapy. Berberine, a plant alkaloid, has been used for fluorescent staining of the Y chromosome. We evaluated whether berberine can be used for staining of malarial parasites in 40 selected peripheral blood smears from patients with clinical symptoms of malaria; smears were evaluated with OptiMal (DiaMed, Miami, FL) and Giemsa stain. Twenty were positive with both OptiMal and Giemsa (Plasmodium vivax, 14; Plasmodium falciparum, 6); 10 were negative with both. The remainder were positive by OptiMal but negative by Giemsa and, therefore, were classified as equivocal. All slides were processed simultaneously, stained with berberine, and read under a fluorescent microscope. P vivax and P falciparum DNA fluoresced with berberine. The positives and negatives by berberine concurred with the Giemsa staining. Of the 10 equivocal smears, 5 were confirmed positive by berberine. Gametocytes were easily identifiable. This test has high sensitivity and high positive predictive value and, once standardized, can be used as a potential screening and diagnostic tool.

Observational therapeutics: Scope, challenges, and organization

The importance of Observational Therapeutics in the progress of medicine has been neglected in the current era of the hierarchal position imparted to Randomized Controlled Trials (RCTs) for new drug discovery and practice of evidence-based medicine. There is a need to reflect on the reason for many new drugs being withdrawn during post marketing surveillance. There are several examples in literature where drug-discovery has originated initially from keen clinical and / or laboratory observations. The roots of these discoveries have often been from observations made by practitioners of traditional medicine including Ayurveda. The present article draws attention to the scope and challenges for observational therapeutics. There is an urgent need for the meticulous planning for a systematic organization of developing observational therapeutics, with a full understanding of its strengths and limitations.

Single dose metformin kinetics after co-administration of nisha-amalaki powder or mamejwa ghanavati, ayurvedic anti-diabetic formulations: A randomized crossover study in healthy volunteers

Objective: The aim was to study herb-drug interaction of two ayurvedic formulations - DMFN01 (Nisha-Amalaki) powder and DMFN02 (Mamejava) ghanavati with metformin at a single dose in healthy volunteers. Materials and Methods: This was an open-labelled, single dose, crossover, and randomized volunteer study. Healthy volunteers were studied in two groups (6/group). Volunteers were randomized to oral metformin (500 mg single dose) alone or with concurrent DMFN01 (10 g), or DMFN02 (750 mg). Venous blood samples were collected at different time points from 0 to 24 h. Plasma metformin concentrations were measured by high performance liquid chromatography coupled with an ultraviolet detector. Results: Simultaneous administration of DMFN01 with metformin showed a reduction in the mean area under the curve (AUC [0-24 h]) of metformin by 51% (P < 0.002) when compared with metformin alone. However, co-administration of DMFN02 did not show any significant difference in the mean AUC of metformin (P = 0.645). One volunteer had a reduction of 41% in AUC of metformin with DMFN 02. Conclusions: These data raise relevant questions on therapeutic control of hyperglycemia when DMFN01 choorna is given concurrently with metformin. Based on known absorption pattern of metformin an interval of 2 h between the oral doses of metformin and ayurvedic formulations would be advisable to avoid interactions. In reverse pharmacological studies, at an early stage, such interaction studies are desirable.

Acharya D. S. Antarkar: A Vaidya with a vision

Dhondo, the eldest son of Sadashiv Antarkar a priest, was born and grew up in a beautiful small village ‘Dugave’ of Ratnagiri district in Maharashtra. The village had a tranquil surrounding and abundant natural wealth. While his two younger siblings were busy playing in the courtyard of their house with make-believe toys made out of mango and jackfruit tree leaves, Antarkar was either engrossed in playing tabla or attempting carpentry. However, very early in life, he had to leave the secure surroundings of his home. He moved to Mumbai with his younger brother as their village provided only primary education. They stayed with their uncle in a joint extended family under one roof, at Worli. He adapted to the transition from a small village with surrounding bountiful greenery to a busy hustle and bustle of a metropolis like Mumbai. Soon he excelled in his studies. At school, he developed an aspiration to be a physician, with an interest in science.

Bone mineral density and reference standards for Indian women.

Many of the published studies from various parts of India, including Ranu Patni’s data, reported in this issue of the JMH, have shown lower values of BMD among young Indian women (when peak bone mass is supposed to be accreted) as compared to those established by the National Health and Nutrition Examination Survey (NHANES) III reference database in women aged 20 – 29 years, as the reference range.[1-3]