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Biomedical subjects

U Patel

Publications and source records attributed to U Patel.

At least 109 records · Page 6Linked to original sources

Synthesis and structure-activity relationship of substituted tetrahydro- and hexahydro-1,2-benzisothiazol-3-one 1,1-dioxides and thiadiazinones: potential anxiolytic agents.

Several novel substituted tetrahydro- and hexahydro-1,2-benzisothiazol-3-one 1,1-dioxides and thiadiazinones were prepared and examined in a series of in vitro and in vivo tests to determine their pharmacological profile. Most compounds were orally active in blocking the conditioned avoidance response (CAR) but did not antagonize apomorphine-induced stereotyped behavior. Several compounds demonstrated moderate to high affinity for the 5-HT1A receptor binding site, with compounds 37 and 38 containing 2-pyrimidinylpiperazinyl and [3-(trifluoromethyl)phenyl]piperazinyl moieties and compound 47 containing the 2-pyrazinylpiperazinyl moiety displaying the highest affinity (Ki values of 10, 4, and 9 nM, respectively). Compound 37, 3-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]hexahydro-4, 7-etheno-1H-cyclobut [f]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide, buspirone, and ipsapirone showed similarities in their neurochemical and behavioral profiles. They were similar in potency in blocking CAR with AB50 values of 39, 32, and 42 mg/kg, respectively. They also demonstrated high affinity and selectivity for the 5-HT1A receptor site (Ki = 10 nM) and exhibited partial agonist/antagonist activity in the serotonin syndrome test. In addition, compound 37 inhibited apomorphine-induced climbing behavior much more potently (ED50 of 3.4 mg/kg) than stereotyped behavior (ED50 of 32.2 mg/kg) and will be evaluated further. Structure-activity relationships within this series of compounds are discussed.

Animals↗

Cervical myelopathy complicating multiple joint replacement in rheumatoid disease.

The incidence of cervical myelopathy and subluxation was investigated in 48 patients with rheumatoid disease who had three or more major lower limb joint replacements. Eight (17%) developed cervical myelopathy requiring cervical fusion. This was the subsequent cause of death in two. Four further patients demonstrated clinical features of myelopathy. Cervical subluxation was present in 29 of 44 (66%) in whom adequate radiographs were available. The development of cervical symptoms and signs could not have been predicted from the sex, age of onset, duration of disease or steroid therapy. Radiographic changes in the cervical spine were independent of major lower limb joint destruction and were often not present when planning a programme of joint replacement. Fifty-one control patients were studied. Cervical myelopathy occurred in 2 (4%) and subluxation in 24 (47%). The development of rheumatoid changes in the cervical spine was unrelated to involvement of the hip or knee joints in the control group. There was a significant (p less than 0.05) increase in the incidence of cervical myelopathy in patients with multiple lower limb joint replacements compared with the control population.

Adolescent↗

Ultrastructure of fetal spinal cord and cortex implants into adult rat spinal cord.

The ultrastructure of cortex and spinal cord from 11-, 12-, and 15-day-old fetuses implanted into the spinal cord of adult rats was studied over 3 months. Under deep Chloropent anesthesia, a 0.5 X 1.0-mm square of fetal cortex or a 1.0-mm segment of fetal spinal cord was implanted subpially between the left dorsal column and the dorsal horn of 70 adult rats. Implants grew toward gray matter, usually interfacing with the host at the isthmus between the horns of the spinal cord. However, implants were observed that occupied the entire left dorsal and ventral horns of the left half of the host spinal cord. Implants had concentric zones: A central zone with basal lamina lined joined channels and subjacent neuroglia; a zone of differentiating implant nervous system; a zone with basal lamina lined implant with overlying pial cells on the dorsal and lateral surfaces of the implant; a zone that interfaced with the host with overlapping neuropil on the lateral and ventral surfaces of the implant. Neuron types were typical for cortical or spinal implants. Implants survived for 3 months and reached stages of neuronal and neuroglial maturation similar to controls. Both fetal spinal cord and brain were successful as implants, had delayed differentiation, and formed complex neuropils. The zone of overlapping interface of the donor and host is an anatomical indication of physiological and functional integration.

Animals↗

Regional differences in cell density and cell genesis in the olfactory epithelium of the salamander, Ambystoma tigrinum.

The olfactory epithelium undergoes continuous regeneration. The present quantitative study uses tritiated thymidine autoradiography to investigate regional differences in the rate of olfactory epithelial cell genesis in the tiger salamander. There was a significant gradient in the incorporation of thymidine from the posterior to the anterior in the nasal cavity: the posterior epithelium underwent cell genesis much faster than the anterior. Additionally, the posterior epithelium was thinner and contained fewer cells than the anterior, although the proportions of receptor, supporting and basal cells remained about the same throughout the epithelium. After 5 or 20 days most of the labelled cells were found in the basal cell layer, although there were a few labelled supporting cells. This confirms observations in other species that there are two populations of dividing cells in the olfactory epithelium: the basal cells which give rise to receptor cells, and the supporting cells. The gradients in epithelial thickness, receptor cells, and the rate of cell genesis parallel a gradient in responsiveness to odorants observed in electrophysiological studies (Mackay-Sim et al. 1982; Mackay-Sim and Shaman 1984). The significance of these anatomical and physiological gradients is presently unclear.

Ambystoma↗

Impaired opsonophagocytosis of serotypes Ib and II of group B streptococci as compared with serotypes Ia and III: role of the alternative pathway of complement in opsonisation of serotype III of group B streptococci.

Using the technique of phagocytic chemiluminescence, we have shown that serotypes Ib and II of group B streptococci are resistant to opsonophagocytosis. The resistant strains became susceptible to opsonophagocytosis by trypsin treatment, but neuraminidase had no effect. Several studies have failed to define a significant role for the alternative pathway of complement in opsonisation of group B streptococci. By simple chelation and heat inactivation studies, we have shown that the alternative pathway of complement is activated by serotype III of group B streptococci.

Adult↗

Non-random distribution of blood vessels in the posterior region of the rat somatosensory cortex.

The quantitative distribution of blood vessels in the barrel region of somatosensory cortex of the rat was studied to determine the relationship of the vascular pattern to a functionally specialized cortical structure. Blood vessels were found to arborize in layers III and IV and to decrease in number toward layers I and VI, creating a spindle-shaped pattern through the cortex. The density of blood vessels was greater in the barrel core versus septal regions of layer IV. The distribution pattern of blood vessels within the barrel region was remarkably non-random and constant even between animals. The pattern was consistent enough to form a reliable set of landmarks with which to identify a specific barrel from light- to electron-microscopy transition.

Animals↗

Growth, differentiation, and viability of fetal rat cortical and spinal cord implants into adult rat spinal cord.

Successful transplantation of the fetal brain into adult host brain has been accomplished. These studies explore the growth, differentiation, and viability of E11, E12, and E15 rat fetal cortex and fetal spinal cord implantation into the spinal cord of adult rats (donor and host, Sprague-Dawley). Under deep Chloropent anesthesia, 70 rats had 1-mm cubes of fetal cortex inserted with pressure or by stylus injection subpially between the dorsal horn and dorsal column (left side), or implantation of whole segments of fetal spinal cord. Animals were prepared for light microscopy 14 and 21 days and 1, 2, and 3 months later. Implants by both fetal tissues had a 69% survival rate. The younger the fetal implant the higher the success of the implant (E11 greater than E15). The diameter of fetal spinal cord implants reached the diameter of control postnatal animals after 30 days. The implants not only increased in mass (up to 7-fold in some cases) but differentiated and matured (apolar, unipolar, bipolar, and multipolar) neurons were observed one to three months postimplantation. By 30 days postimplantation, fetal neurons had large, often crenated nuclei, with a large single prominent nucleolus. The most successful implants were the young E11 fetal spinal cord into the adult host spinal cord. These implants represent an initial successful transplantation of fetal spinal cord into adult spinal cord.

Animals↗

Clinical and pharmacokinetic evaluation of moxalactam in infants and children.

Moxalactam, a new beta-lactam antibiotic was evaluated in the treatment of 21 pediatric patients including 16 with clinical and radiological evidence of pneumonia and 5 with urinary tract infection (UTI). Clinical and radiological resolution of pneumonia occurred in all. Bacteriological efficacy in pneumonia, however, was assessed in only 1 patient whose blood culture grew H. influenzae type b. In patients with UTI, the therapy was successful, bacteriologically as well as clinically. The only side effects observed were mild transient elevation of SGOT and alkaline phosphatase in 6 cases. The peak and trough levels of the drug were manyfold higher than the known minimum inhibitory concentrations of common pathogens. The mean t1/2 projected of 95 and 124 min with intravenous and intramuscular route, respectively, were similar to those reported in adults.

Adolescent↗

Hormonal factors concerned with liver regeneration.

Hepatic regeneration in partially hepatectomized, eviscerated rats, and survival in mice infected with lethal doses of murine hepatitis virus, are both strikingly promoted by combined administration of insulin and glucagon. These two hormones, although potent promotors, fail as initiators of hepatocyte proliferation in animals with intact liver, which suggests a requirement for additional factors, probably derived from non-portal-splanchnic organs. We now find that continous intraperitoneal infusion of epidermal growth factor (EGF) initiates DNA synthesis, as determined by incorporation of [3H] thymidine, in livers of adult rats in vivo. The rise in DNA labelling, which is small with EGF alone, is augmented by addition to the infusion of either glucagon or insulin. This is in agreement with reports on adult hepatocytes in culture. Whether EGF has a physiological role in regulating liver growth under normal conditions in vivo remains to be determined.

Age Factors↗