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Biomedical subjects

S R Khan

Publications and source records attributed to S R Khan.

At least 19 recordsLinked to original sources

Acute hyperoxaluria, renal injury and calcium oxalate urolithiasis.

Single intraperitoneal injections of three, seven, or 10 mg. of sodium oxalate per 100 gm. of rat body weight were administered to male Sprague-Dawley rats. At various times after the injection, urine samples were analyzed for oxalate, and urinary enzymes, alkaline phosphatase, leucine aminopeptidase, gamma-glutamyl transpeptidase, and N-acetyl-beta-glucosaminidase. The kidneys were processed for light microscopy and renal calcium and oxalate determination. Oxalate administration resulted in an increase in urinary oxalate and formation of calcium oxalate crystals in the kidneys. The amount and duration of urinary excretion of excess oxalate and retention of crystals in the kidneys correlated with the dose of sodium oxalate administered. At a low oxalate dose of three mg./100 gm., crystals moved rapidly down the nephron and cleared the kidneys. At higher doses crystals were retained in kidneys and at a dose of 10 mg./100 gm. were still there seven days post-injection. Crystal retention was associated with enhanced excretion of urinary enzymes indicating renal tubular epithelial injury.

Acute Disease

Structure of rat kidneys following microwave accelerated fixation.

In contrast to fixation of tissue in externally heated fixative, microwave-irradiation can generate uniform internal heat, which is of utmost importance for successful fixation of biological tissue. To evaluate the effectiveness of microwave-accelerated chemical fixation, we compared the structure of rat kidney fixed by a conventional method and a microwave-accelerated method, by scanning and transmission electron microscopy. Following perfusion, rat kidney pieces 1-2 mm in size were irradiated in Karnovsky's fixative in a domestic Amana microwave oven, till the temperature of the fixative reached 45-50 degrees C. For conventional fixation, tissue pieces were fixed overnight at room temperature in the same fixative. Both types of samples were processed further for electron microscopy using identical protocols. The microwave fixed samples showed excellent preservation of structure comparable to the samples fixed by the conventional method. Glomeruli and the renal tubules showed normal morphology with no cellular swelling. The cytoplasm and nuclear matrix of the epithelial cells was uniformly dense. Other fixation sensitive organelles like mitochondria and Golgi apparatus showed superior preservation with continuous membranes. These results demonstrate that microwave accelerated chemical fixation results in excellent preservation of tissue structure, reduces processing time significantly and is therefore a practical alternative to conventional protocols.

Animals

Effect of magnesium on calcium oxalate urolithiasis.

Previous studies have shown that hypomagnesuria induced by magnesium deficient diet causes calcium oxalate crystal deposition in renal tubules of hyperoxaluric rats and administration of magnesium to these rats results in prevention of calcium oxalate crystallization in their kidneys. Based on these studies magnesium was claimed to be beneficial for calcium oxalate stone patients. However, hypomagnesuria is not a common phenomenon. To better understand the role of magnesium as an inhibitor of calcium oxalate crystallization in urine, we studied the effect of magnesium on calcium oxalate urolithiasis in rats on a regular diet and a hyperoxaluric protocol. Excess magnesium was administered to male rats on regular diet and a lithogenic protocol. Magnesium administration to hyperoxaluric rats did not result in significant changes in urinary excretion of calcium or oxalate or in calcium oxalate relative supersaturation. Urinary excretion of citrate was also not significantly altered. Some animals from both groups, those on magnesium therapy and those not on magnesium therapy had crystals deposited in their renal tubules. We conclude that excess magnesium has no significant effect on calcium oxalate urolithiasis in normomagnesuric conditions.

Animals

Pathogenesis of oxalate urolithiasis: lessons from experimental studies with rats.

Calcium oxalate (CaOx) urolithiasis in rats is induced by producing hyperoxaluria. Depending on the degree and length of hyperoxaluria, CaOx crystals may either form in the nephron or the bladder and may or may not be retained in the kidneys. Crystals may nucleate in one part of the nephron and be retained in another part. Papillary collecting duct tubular epithelium and its basement membrane appear to be involved in crystal retention in the kidneys.

Animals

Breast feeding and protection against neonatal sepsis in a high risk population.

Protection against neonatal sepsis by breast feeding was investigated in a developing community. A case-control study was carried out with 42 cases from a hospital and 270 controls, matched for age and socioeconomic conditions from the community. Exclusive breast feeding was extremely rare, most babies being partially breast fed and a few being given formula feed or animal milk. A highly significant odds ratio of 18 was obtained, showing that even partial breast feeding protects against neonatal sepsis in such a population.

Bacterial Infections

Retention of calcium oxalate crystals in renal tubules.

Crystal retention within the renal tubules is essential for nephrolithiasis and the development of urinary stone disease. We studied the mechanisms involved in this process by inducing calcium oxalate crystal deposition within the rat renal tubules and examining them using various microscopic techniques. Crystals appeared to be retained either by attachment to the tubular epithelium or by aggregating with other crystals thus becoming large enough to be retained by their collective size.

Animals

Studies on the prospect of bioprostheses by bovine aortic valve for human use.

A total of 21 heart specimens from indigenous cattle (Bos indicus) were studied. The measurement and observation of bovine heart and aortic valve in different age group is the preliminary finding of this research work. After harvesting, the bovine aortic valves were measured and the sizes ranged from 21 mm to 35 mm in orifice diameter. In comparison with implanted aortic and mitral valves at NICVD in 1989, it indicates that the selected bovine heart valves (specially aortic valves) were similar to human valve size and can be used in future for implantation as far as the size is concerned. Now further study regarding making these tissue valves implantation worthy for clinical use is to be undertaken. We strongly feel the prospect is bright.

Animals

Prophylactic glutamine protects the intestinal mucosa from radiation injury.

Glutamine may be an essential dietary component, especially for the support of intestinal mucosal growth and function. This study evaluated the effects of a glutamine-enriched elemental diet, administered before whole-abdominal radiation on gut glutamine metabolism, mucosal morphometrics, and bacterial translocation. Rats were randomized to receive a nutritionally complete elemental diet that was glutamine-enriched or glutamine-free for 4 days. The animals were then subjected to a single dose of 1000 cGy x-radiation to the abdomen. After irradiation, all animals received the glutamine-free diet. Four days later the animals underwent laparotomy for sampling of arterial and portal venous blood, culture of mesenteric lymph nodes, and removal of the small intestine for microscopic examination. There was no difference in arterial glutamine or gut glutamine extraction between the two groups, but body weight loss was significantly diminished in the glutamine-fed rats. Rats receiving the glutamine-enriched elemental diet before radiation had a significant increase in jejunal villous number, villous height, and number of metaphase mitoses per crypt. Scanning electron microscopy confirmed the presence of an intact gut epithelium in eight of eight rats receiving prophylactic glutamine compared to one of eight animals in the glutamine-free group. Three of eight rats fed glutamine had culture positive mesenteric lymph nodes compared with five of seven rats receiving the glutamine-free diet. Glutamine exerts a protective effect on the small bowel mucosa by supporting crypt cell proliferation effect on accelerate healing of the acutely radiated bowel.

Animals

Dextran sulfate disposition in the rat.

Comparative studies of oral and intravenous administration of tritiated dextran sulfate in rats showed markedly different distribution patterns. Following IV dosing about 50 per cent of the radioactivity was recovered in feces and urine within 24 h. The major portion of the recoverable dose was eliminated in the urine as dextran sulfate within 3 h after administration. In orally treated rats only about 32 per cent of the 3H was recovered in the feces and urine, the major fraction being associated with unabsorbed dextran sulfate in the feces. The remainder of the dose in both treatment groups has apparently distributed throughout the rat body with some accumulation in the liver, kidney and spleen. Consequently, the disposition of about 67 per cent or the oral dose could not be fully accounted for by these excretion routes. However, separation with Sephadex columns showed similarities in the 24 h plasma and urine profiles of the IV and orally dosed rats which suggest that while the oral dose was absorbed as dextran sulfate, it underwent rapid metabolism to small molecular weight products prior to entering the systemic circulation which were then widely distributed within the rat.

Administration, Oral

Membrane-associated crystallization of calcium oxalate in vitro.

Incubation of proximal tubular brush border membrane in a metastable calcium oxalate solution of low supersaturation resulted in the equimolar depletion of calcium and oxalate and the formation of monoclinic calcium oxalate crystals. We propose that membrane fragments from sloughed epithelial cells of the nephron can similarly induce crystallization in urine that is metastable for calcium oxalate.

Animals

Cell injury associated calcium oxalate crystalluria.

Renal tubular cell damage, resulting in membranuria, was induced by the administration of subcutaneous gentamicin to male Sprague-Dawley rats. One group of rats received gentamicin only, while a second group was given gentamicin plus ethylene glycol in drinking water at a concentration which increased urine oxalate but alone did not cause calcium oxalate crystalluria. Crystalluria occurred early in the combined treatment groups and persisted for the duration of the experiment. Crystalluria was not present in animals receiving gentamicin or ethylene glycol only. These results suggest that cellular fragments can serve as heterogeneous foci for the nucleation of calcium oxalate crystals.

Animals

Bladder stone in a human female: the case of an abnormally located intrauterine contraceptive device.

A single 4.7 x 3.3 x 1.5 cm solid nodule was removed from the bladder of a 24 years old white female who had lost an intrauterine contraceptive device (IUD) installed approximately four years ago. The nodule showed no external evidence of an IUD or its string. An examination of the nodular surface by scanning electron microscopy (SEM) showed mostly amorphous material with some adherent filamentous structures. Its energy dispersive x-ray microanalysis revealed the presence of calcium and phosphorus suggesting that the nodule was actually a urolith. Fracturing the nodule exposed an embedded entity consistent with being a copper IUD. Apparently, the lost IUD had migrated from the uterus into the bladder where it became mineralized. Thus the solid nodule was actually a foreign body stone.

Adult

Urinary enzymes and calcium oxalate urolithiasis.

Male Sprague-Dawley rats were challenged with various hyperoxaluric agents including ammonium oxalate, hydroxy-L-proline, and ethylene glycol. All treatments resulted in increased urinary oxalate. Associated with hyperoxaluria was an increase in urinary levels of renal enzymes, gamma-glutamyl transpeptidase, N-acetyl-beta-glucosaminidase, and alkaline phosphatase. Most of the rats did not demonstrate any significant change in urinary levels of beta-galactosidase. There was a highly significant positive correlation between urinary oxalate and N-acetyl-beta-glucosaminidase.

Acetylglucosaminidase

Intestinal permeability assessed with polyethylene glycols in children with diarrhea due to rotavirus and common bacterial pathogens in a developing community.

Intestinal permeability was assessed with different-sized polyethylene glycols (PEG 400 and PEG 1,000) in small children with acute diarrhea. All children with acute diarrhea absorbed and excreted less PEG of all molecular sizes into the urine when compared with healthy control children (p less than 0.001). Children with acute rotavirus infection excreted significantly less PEG of all sizes than children with Shigella, Salmonella, and enteropathogenic Escherichia coli (EPEC) infection (p less than 0.001-0.01), suggesting a more severe mucosal lesion caused by rotavirus. In patients with severe malnutrition there was also a significant decrease in absorption of PEGs observed. In addition, malnourished patients with rotavirus diarrhea showed a pronounced decrease of PEGs in comparison with well-nourished patients. The ratio between the recovery of a large PEG molecule, 1,074 Da, and a small molecule, 370 Da, was utilized to assess the absorption of large molecules in relation to that of smaller ones. On applying this ratio, it was noted that the intestine in children with Shigella and EPEC infection was relatively more permeable to larger molecules than in healthy controls, while in rotavirus and Salmonella infection it was less permeable to larger molecules. In this study significant differences in the permeability characteristics were observed, suggesting etiology-specific effects on the mucosal barrier.

Child, Preschool

Paralytic ileus, a serious complication in acute diarrhoea disease among infants in developing countries.

Intestinal hypomotility is a common late complication in infants with acute diarrhoeal disease in pakistan. Among the infants admitted to our gastrointestinal unit with a history of acute diarrhoea, 35% developed abdominal distension and 12% developed the full clinical picture of paralytic ileus. The infants with ileus were treated with decompression and total parenteral nutrition; in this group the mortality rate was 25%. We compared 30 infants who developed ileus (group A) with an age-matched control group of infants (group B) who were admitted because of acute diarrhoea but did not develope ileus. The use of antimotility drugs was significantly more frequent in group A. Serum-K was not different in in group A (3.92 +/- 0.22 mmol/l) and group B (4.32 +/- 0.18 mmol/1). However, there were more patients who had serum-K below 3 mmol/l in group A (8/30) than in group B (5/30). We conclude that the use of antimotility drugs predisposes to the development of ileus in infants with acute diarrhoea. Hypokalemia may contribute to ileus in a few cases but is generally not a prerequisite.

Acute Disease

Presence of lipids in urinary stones: results of preliminary studies.

The presence of lipids in urinary stones was determined by histochemical and biochemical methods. When crystals of calcium oxalate, made by mixing calcium chloride and potassium oxalate solutions and sections of human calcium oxalate urinary stones, were exposed to osmium vapors, there was no staining of the pure crystals whereas the stone sections were stained. De-paraffinized sections of demineralized calcium oxalate stones showed positive sudanophilia on staining with Sudan black B. Both these experiments indicate the presence of lipids in calcium oxalate stones. Lipids were extracted from uric acid, struvite, and calcium oxalate stones using standard techniques. Phospholipids were separated by one-dimensional thin layer chromatography. All the stones studied contained lipids. In calcium oxalate stones they accounted for 10.15% of the matrix. Calcium oxalate and struvite stones contained more phospholipids than uric acid stones. Cardiolipin, sphingomyelin, phosphatidyl choline, phosphatidyl inositol, phosphatidyl ethanolamine, phosphatidyl serine, and phosphatidyl glycerol were identified in lipid extracts. Demineralization by ethylenediaminetetra-acetate (EDTA) treatment increased lipid output from calcium oxalate stones by 15.5%.

Calcium Oxalate