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Biomedical subjects

O P Sharma

Publications and source records attributed to O P Sharma.

At least 19 recordsLinked to original sources

Biological action of lantadene C, a new hepatotoxicant from Lantana camara var. aculeata.

Lantadene C (22 beta-2-methylbutanoyloxy-3-oxoolean-12-en-28-oic acid) isolated from the leaves of the hepatotoxic plant Lantana camara var. aculeata (Red) has been found to be identical with dihydrolantadene A reported earlier. Molecular structure of lantadene C has been deduced from single crystal X-ray diffraction analysis. It resembles lantadene A in the pentacyclic portion of the molecule but differs in the side chain region. Atom C-34 is cis to C-35 in lantadene C but is trans in lantadene A. Semisynthetic lantadene C was prepared by catalytic hydrogenation of lantadene A. Lantadene C was obtained in two forms, I and II. Form I was crystalline while form II was amorphous. Unlike lantadene A, both form I and II of lantadene C elicited strong hepatotoxic response in guinea pigs associated with decrease in fecal output, feed intake, hepatomegaly, hepatic injury at the cellular and subcellular level, increase in plasma bilirubin, and acid phosphatase activity. All the clinical signs, hepatic lesions, and changes in blood plasma typified lantana toxicity. This is the first report on the hepatoxicity of lantadene C. The interrelation of molecular structure and biological activity of lantadene A and C has been discussed.

Acid Phosphatase

The gonadotropin-releasing hormone (GnRH) agonist-induced initial rise of bioactive LH and testosterone can be blunted in a dose-dependent manner by GnRH antagonist in the non-human primate.

Gonadotropin-releasing hormone (GnRH) agonists induce a clinically undesirable, transitory but very pronounced initial rise of gonadotropin and gonadal steroid secretion. We investigated, in a non-human primate model, whether the initial stimulatory effects of GnRH agonists can be avoided by a short period of pretreatment and simultaneous treatment with a GnRH antagonist. Three groups of five adult male cynomolgus monkeys (Macaca fascicularis) received a single s.c. biodegradable implant loaded with the GnRH agonist, buserelin ([D-Ser(TBu)6-desGly-NH2]-GnRH), releasing approximately 50 micrograms buserelin daily. From 1 week before to 1 week after inception of administration of GnRH agonist, group 1 received the GnRH antagonist vehicle, and groups 2 and 3 were given s.c. injections of the GnRH antagonist Nal-Glu ([Ac-D-Nal(2)1,D-4-Cl-Phe2,D-Pal3,D-Arg5,D-Glu6(AA),D- Ala10]-GnRH) at a dose of 450 or 2250 micrograms/kg daily. In the absence of GnRH antagonist, the GnRH agonist induced a marked elevation of serum luteinizing hormone (LH) and testosterone lasting for 2 and 5 days, respectively. In group 2, Nal-Glu reduced basal hormone secretion and delayed the peak of GnRH-agonist-induced hormone secretion by 1 day. In group 3, the GnRH-agonist-induced rise of LH and testosterone was prevented in three animals and did not exceed baseline hormone levels in the other two animals. Areas under the LH and testosterone curves were significantly reduced in group 3 compared to group 1. After withdrawal of the GnRH antagonist, a second transient rise of hormone secretion was observed. Except for testosterone in group 2, this rise did not exceed the baseline range of hormone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Soy of dietary source plays a preventive role against the pathogenesis of prostatitis in rats.

This study examined the effects of diet on the development of prostatitis in male rats. Adult male rats were placed on either of two specially formulated diets which differed from one another by the presence or absence of soy as the protein source. A third group of rats (control) was fed standard laboratory rat chow which also includes soy as a source of protein. After 11 weeks, it was found that rats maintained on soy-free diet developed prostatitis mainly in the lateral lobe of the prostate. Increased severity and incidence of prostatitis in rats maintained on the soy-free diet coincided with a significant decrease in urinary excretion of various phytoestrogens. There was no evidence of prostatitis in rats maintained on soy-containing diets. Urinary excretion of phytoestrogens in rats maintained on soy-containing diet was also not different from controls. These results suggest that soy as a dietary source plays a protective role against the development of prostatitis in rats, and indicate that the ventral, lateral and dorsal lobes of the rat prostate have different sensitivities to alterations in dietary factors.

Animals

Macrodystrophia lipomatosa: radiographic observations.

23 cases of macrodystrophia lipomatosa (MDL) are reported showing a wide spectrum of radiographic findings. Typical findings were hypertrophy of all the mesodermal tissues of the affected digits with dramatic overgrowth of fat. Phalanges were enlarged both in length and transverse diameter, but the trabecular pattern was maintained. In one patient, the phalanges and metatarsals were elongated but thinned. In another case, all the phalanges and metatarsals of the great toe were small. The little toe was also involved in two cases. Articular surfaces were slanting. There was a high incidence of palmar and plantar involvement. In a few cases the forearm and leg were also involved. Other uncommon features observed were early maturation of epiphyseal centres of ossification of phalanges and metatarsals, syndactyly, polydactyly, brachydactyly and symphalangism. Angiography was uncharacteristic.

Adolescent

Eflornithine treatment of refractory Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome.

Eflornithine was offered as compassionate treatment of 33 episodes of Pneumocystis carinii pneumonia in 31 patients with acquired immunodeficiency syndrome who were intolerant of and/or unresponsive to conventional trimethoprim-sulfamethoxazole or pentamidine therapy. A full course of eflornithine consisted of ten days at 400 mg/kg/d but no more than 30 g/d in four divided intravenous doses, four days at 300 mg/kg/d in four divided intravenous doses, and then up to six weeks at 300 mg/kg/d in four divided oral doses where tolerated. Of 33 patient-episodes, 15 patients were discharged from the hospital without need for supplemental oxygen after receiving ten or more days of parenteral therapy and were classified as responders. Of the 16 episodes classified as treatment failures, death occurred within the first 10 days of therapy in 12, and supplemental oxygen could not be withdrawn in 4. The other two patients left the hospital without need of oxygen after receiving one and six days of treatment with eflornithine and were not considered evaluable for efficacy. The most serious adverse effect was thrombocytopenia, which occurred in 12 of 19 patients treated for ten days or more. Serious bleeding associated with thrombocytopenia was observed in two patients. Other common adverse effects were anorexia, nausea, and diarrhea. Prior to receiving eflornithine, 13 of 15 responders had received ten or more days of conventional therapy without demonstrating clinical improvement. Two had improved while receiving conventional therapy but were switched to eflornithine because of a treatment-limiting adverse effect of standard therapy. These results suggest that eflornithine may be useful as an alternative therapeutic agent for Pneumocystis carinii pneumonia. Studies designed to determine proper dosage, duration of therapy, and efficacy as primary therapy are warranted.

Acquired Immunodeficiency Syndrome

Abnormal oxygen uptake responses to exercise in patients with mild pulmonary sarcoidosis.

Exercise intolerance and exertional dyspnea are common complaints in patients with sarcoidosis. Although in many cases these complaints are attributable to restrictive or obstructive lung mechanics or inefficiency of pulmonary gas exchange, other processes also may contribute to impairment in exercise function and may not be readily detected or distinguished from problems of lung mechanics on the basis of symptoms or routine laboratory testing. To identify the frequency and etiology of impaired exercise capacity in sarcoidosis patients with mild lung disease, integrative cardiopulmonary exercise testing was performed in 23 patients. Breath-by-breath measurements were made of gas exchange, ventilation, and heart rate. In 9 of 20 evaluable patients, the oxygen uptake (VO2) at the anaerobic threshold was low, and/or the rate of increase of VO2 was abnormal relative to work rate or heart rate, suggesting a defect in cardiocirculatory function. Resting and exercise echocardiography revealed normal left ventricular ejection fractions and wall motion in all nine of these patients, but findings suggestive of right ventricular hypertrophy and/or right ventricular dysfunction were present in five. Abnormal responses of VO2 during exercise are common in patients with sarcoidosis and may be due to subclinical impairment of right-sided cardiac function.

Adult

Bronchopulmonary lavage (BAL). A window of the lungs.

Bronchopulmonary lavage (BAL) has provided a fresh dimension for the investigation of pulmonary and multisystem disorders. BAL fluid may be analysed for cells and chemical mediators in the diagnosis and also serially for the management of several granulomatous disorders including sarcoidosis, extrinsic allergic alveolitis, chronic beryllium disease, talc granulomatosis, tuberculosis, Langerhans' histiocytosis-x and Crohn's disease. It may also provide information in fibrosing alveolitis, collagen vascular disease, occupational and drug-induced lung disease, acquired immune deficiency syndrome, bronchial asthma, neoplasia, transplantation, pulmonary alveolar proteinosis and eosinophilic lung disease. This survey analyses the value of BAL and how it has provided a new window for the chest physician.

Bronchoalveolar Lavage Fluid

CT staging of pancreatic and periampullary carcinoma.

Sixteen cases of carcinoma head pancreas and seven cases of periampullary carcinoma are staged together on CT scan because of their morphological similarity and similar parameters. Following parameters are considered for CT staging: tumour mass, involvement of splanchnic vessels, locoregional lymph nodes and presence or absence of hepatic metastases. Findings were confirmed on surgical exploration. A contrast enhanced CT scan was 58.3 percent sensitive and 100 percent specific for the involvement of lymph nodes and 100 percent sensitive and 93.4 percent specific for hepatic metastases. The cases diagnosed as non-resectable on CT staging were found inoperable on exploration. Authors believe that for all practical purposes, pancreatic and periampullary malignancies can be grouped together and a contrast enhanced CT scan can provide reliable information for the staging of the tumor.

Ampulla of Vater

Molecular structure, polymorphism, and toxicity of lantadene A, the pentacyclic triterpenoid from the hepatotoxic plant Lantana camara.

Lantadene A (22 beta-angeloyloxy-3-oxo-olean-12-en-28-oic acid), a pentacyclic triterpenoid compound from lantana (Lantana camara) leaves has been obtained in two polymorphic forms I and II. Form I had white, fluffy, and rod-shaped uniform crystals. Form II particles were irregular, shining, and polyhedral. The two forms differed in melting behavior. The powder x-ray diffraction of form I showed sharp peaks whereas from II did not contain distinct peaks. From single-crystal three-dimensional x-ray structure determination, the molecular structure of form I has been established. A/B and B/C rings of the molecule are trans fused while D/E rings are cis fused. The packing of the molecule is stabilized by hydrogen bonding. Form I of lantadene A was non-toxic to guinea pigs on oral administration. Form II induced ictericity and toxicity associated with decrease in feed intake and fecal output, hepatomegaly, increase in plasma bilirubin, and acid phosphatase activity.

Animals

The enzymatic profile of urine and plasma in bovine urinary bladder cancer (enzootic bovine haematuria).

The enzymatic profile of urine and plasma in field cases of bovine bladder cancer was studied. Urinary lactate dehydrogenase activity was significantly altered along with the isoenzyme pattern. Activity of alkaline phosphatase and beta-glucuronidase was decreased in the affected animals. No significant changes were observed in acid phosphatase, or arylsulphatase A and B activity. In plasma, lactate dehydrogenase activity was elevated without any change in the isoenzyme pattern. No significant changes were observed in the other plasma enzymes studied or in the sialic acid concentration.

Alkaline Phosphatase

Hypersensitivity pneumonitis.

Hypersensitivity pneumonitis or extrinsic allergic alveolitis is an immunologically mediated lung disease caused by repeated inhalations of organic antigens. The basic histologic lesion consists of a diffuse mononuclear cell infiltration of alveolar wall, alveoli, terminal bronchioles, and neighboring interstitium. The inflammation is often followed by granulomas, which then may progress to fibrosis. Although there is no single radiologic, physiologic, or immunologic test specific for hypersensitivity pneumonitis, the diagnosis can often be suspected on the basis of a compatible temporal relationship of pulmonary symptoms to the history of environmental or occupational exposure. Once the diagnosis is suspected, the presence of serum precipitating antibodies (IgG), suppressor cytotoxic lymphocytosis in bronchoalveolar lavage fluid, and granulomatous alveolitis in lung biopsy specimens are extremely helpful in confirming the diagnosis. In patients where the diagnosis is confirmed, avoidance of the causative antigen is the best therapy, although corticosteroids are used to suppress inflammation. Once the fibrosis is set in, the patient may gradually slide into respiratory failure, cor pulmonale, and death.

Allergens