Double-blind crossover comparison of amlodipine at three dose levels and placebo in chronic stable angina.
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Biomedical subjects
Publications and source records attributed to S Das.
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The effect of chronic administration of morphine and subsequent withdrawal on brain and pituitary receptors for thyrotropin releasing hormone (TRH) was investigated in Sprague-Dawley rats. The rats were implanted subcutaneously with four morphine pellets (each containing 75 mg of morphine free base) during a 3-day period. Placebo pellets, which contained all the excipients of morphine pellets except the morphine, were implanted in rats which served as controls. Both tolerance and physical dependence on morphine have been shown to develop as a result of this procedure. TRH receptors were labeled with 3H-(3-MeHis2) TRH (MeTRH). 3H-MeTRH bound to brain membranes at a single high affinity site with Bmax (receptor density) value of 24.6 +/- 2.2 fmol/mg protein and Kd (apparent dissociation constant) value of 3.7 +/- 0.4 nM. The binding of 3H-MeTRH to five regions of the brain namely, hypothalamus, cortex, striatum, midbrain and pons + medulla, as well as pituitary was also investigated. The binding of 3H-MeTRH to pituitary membranes was increased during the development of tolerance, whereas the binding to membranes prepared from different brain regions was unaffected. Serum concentration of triiodothyronine (T3) and thyroxine (T4) were found to be lower in chronic morphine-treated rats when compared to placebo-treated rats, however, serum TSH level remained unaltered. Twenty-four hours after the removal of morphine pellets (natural withdrawal), the binding of 3H-MeTRH to pons + medulla membranes was greater than in placebo control group. Naloxone-precipitated withdrawal produced results which were qualitatively similar to those obtained in rats from which pellets had been removed. The results suggest that the development of tolerance to morphine may be associated with changes in the pituitary-thyroid axis.
Ionomycin, which activates the Ca2+-calmodulin system, and phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (PKC), were used to investigate potential roles of these systems as mediators of the biphasic secretion of luteinizing hormone. Quartered pituitaries from diestrous II female rats were perifused at 37 degrees C, and sequential effluent fractions collected every 10 min. Gonadotropin-releasing hormone administration resulted in a biphasic response: an initial, protein synthesis-independent secretion, followed 60 min later by a secondary, augmented, protein synthesis-dependent component. Ionomycin-stimulated gonadotropin secretion was immediate and partially independent of protein synthesis, whereas the PMA-induced secretion was delayed (approximately 70 min), and was completely dependent on protein synthesis. Simultaneous infusions of ionomycin and PMA resulted in an initial, protein synthesis-independent response followed by the secondary, augmented, protein synthesis-dependent component, which exhibited synergistic interactions between calmodulin and PKC. These results suggest that calmodulin mediates the initial, protein synthesis-independent secretion, PKC mediates part of the secondary, augmented response, while calmodulin and PKC synergize to mediate the remaining component of the secondary response.
Phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (PKC) was used to investigate the estradiol dependency of PKC-stimulated luteinizing hormone (LH) secretion from perifused anterior pituitaries. Infusions of PMA stimulated LH secretion from diestrous II, ovariectomized + estradiol-treated, and orchidectomized + estradiol-treated quartered pituitaries, by protein synthesis-dependent mechanisms. In contrast, pituitaries from intact, orchidectomized males, or ovariectomized females were unresponsive to PMA. Interestingly, dispersed male pituitary cells differed from male pituitary tissue blocks, in that the dispersed cells responded to PMA with increased LH secretion. These results indicate that PKC's ability to directly stimulate LH secretion is dependent on de novo protein synthesis and estradiol. Moreover, the effects of estradiol on PKC-stimulated secretion form at least one basis for the estradiol-induced increased responsiveness of gonadotrophs to GnRH. Additionally, it appears that dispersed pituitary cells may not respond to activators of PKC in a physiological manner.
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A spectrophotometric procedure for the simultaneous determination of mefenamic acid and paracetamol in a mixture is described. Using 0.01 M methanolic hydrochloric acid as solvent, the absorbance of the mixture is measured at 248, 279 and 351 nm. The concentration of each component can be calculated by solving two equations using two wavelengths, either 248 and 279 nm or 248 and 351 nm.
Anterior urethral valves are rare anomalies which cause obstructive uropathy in the lower urinary tract of young men. We discuss our illustrative case and review the English medical literature in order to analyze the clinicopathologic spectrum. We propose a hypothesis of embryology of this lesion and present guidelines for its management.
We present an unusual case of proximal extrusion of a semirigid penile prosthesis into the gluteal subcutaneous tissue. The possible causes, prevention, and treatment options of this uncommon complication are discussed.
We report a case of Balo's concentric sclerosis, a rare and acute variant of multiple sclerosis, which coexisted with an oligodendroglioma. The demyelinating lesion was clinically silent and was detected at necropsy. The pathogenesis of concentric sclerosis and the relationship of the demyelinating lesion to the evolution of the glial neoplasm is briefly discussed.
The skin is rather an unusual site of metastasis from carcinoma of the rectum. When the skin is involved, it tends to be part of the picture of widespread terminal malignant disease. Consequently, survival after the appearance of skin metastases is usually short. It is uncommon for skin metastases to be a presenting feature, and especially so if the involved skin is on the distal part of a limb. We would, therefore, like to present such a case.
The precipitation of cholesterol dissolved in organic solvents, viz. methanol, ethanol, n-propanol, isopropanol, acetone and 1,4-dioxane, by the addition of water has been studied. The effects of the solvents towards the precipitation follow the order: methanol greater than ethanol greater than acetone greater than dioxane greater than n-propanol greater than iso-propanol, the solvent dioxane however exhibits a change in the order at higher concentration. Additives like Triton X-100, sodium cholate, sodium deoxycholate, sodium dehydro cholate, sodium salicylate and sodium chloride have some protective action against precipitation, the maximum protection being that of Triton X-100. The additives have shown better protective action in propanols and dioxane than in methanol, ethanol and acetone. Analysis of solvent composition and dielectric constant has revealed specific solvent effects on the water-induced precipitation of cholesterol. Thermodynamic analysis of the precipitation phenomenon and the unique role of solvent structure on cholesterol precipitation has been discussed.
A new, sensitive and convenient ELISA method has been developed for quantitation of tubulin using poly-1-lysine (PLL) coated multiwell microtiter plates. Binding of tubulin to untreated plastic surface of microtiter plates was extremely poor. Coating of wells with PLL enhanced the binding and facilitated quantitation by ELISA. Binding of tubulin was followed by stepwise additions of rabbit anti-tubulin IgG, HRP-conjugated goat anti-rabbit IgG and colour reagent. The method has been successfully applied to quantitate the tubulin content of extracts from rat brain and liver as evident from the excellent correlation of the results with those obtained from 3H-colchicine binding assay. The detection limit is as low as 5 ng, which is relatively better than that of the previous RIA methods. The ELISA method does not involve the use of any radioactive compound and all reagents required for this assay are commercially available.
Spectrophotometric and spectrofluorometric titrations of two strongly aggregating dyes, 1,9-dimethylmethylene blue (DMMB) and acridine orange (AO), by three anionic biopolymers, chondroitin sulphate A, DNA and teichoic acid (TA), have been described. Though the three polymers differ in their dye binding efficiencies and TA is a weak chromotrope, the equivalent weights of the polymers can be estimated accurately by these methods using the two dyes. Results show DMMB to be the preferred dye for spectrophotometric titration. The titrations can be used to estimate the equivalent weights of anionic polymers, and also for the quantitative estimation of such polymers of known equivalent weights.
The biopsy material obtained from lesions of CNS are subjected to squash smear technique for rapid diagnosis as it is easier to make and the cytological features of cells are well preserved. During the year 1982-1983 one hundred and seventy eight squash smears were made to offer rapid diagnosis to the operating surgeon. The diagnosis was verified on paraffin sections. Correct diagnosis was made in 87% of cases. Various lesions have distinct cytomorphological features on smears. These distinct characters and efficacy of the method are discussed.
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Cholesterol content of major lipoprotein fractions along with total cholesterol (Tc) and triglyceride (Tg) were measured in 65 samples from 35 women using levonorgestrel contraceptive implant, Norplant-2 from the third month of implantation until the end of second year along with twenty-five healthy controls. There were significant decreases in all the fractional lipid values, Tc and Tg, up to the sixth month followed by a gradual rise of all lipid parameters except HDLc which remained much below the control level. Interestingly, VLDLc exhibited a significant rise at the end of the second year.
The present study was undertaken to investigate the effects of sex and estrous cycle on the manifestation of the extracellular Ca2+-independent component of gonadotropin secretion. Quartered pituitaries from male, ovariectomized (OVX) females +/- estradiol (E2) implants, and mature females at each stage of the estrous cycle were perifused with Ca2+-free medium. Gonadotropin releasing hormone (GnRH)-stimulated luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion from male and OVX pituitaries was inhibited in Ca2+-free medium. In contrast, only a partial inhibition was obtained from OVX + E2 or regularly cycling female pituitaries. This extracellular Ca2+-independent component of gonadotropin secretion was lowest at estrus and increased progressively during the estrous cycle. Estradiol replacement in OVX animals resulted in a response similar to that obtained on proestrus. These results indicate that the extracellular Ca2+-independent component of LH and FSH release is only manifest from intact female and not male pituitaries, and is dependent on estradiol.