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Biomedical subjects

S Batra

Publications and source records attributed to S Batra.

At least 91 records · Page 5Linked to original sources

The capillarity of the subendocardium of left ventricle in rats reared at a low temperature for many generations.

The cardiac capillarity in adult rats reared at 5 degrees C for 68 generations was studied with a double staining method of alkaline phosphatase and dipeptidylpeptidase IV. Capillary density, proportions of arteriolar, intermediate and venular capillary portions and capillary domain area were measured in the left ventricular wall. Compared with the control rats which had been brought back from the low temperature at the 12th generation and reared at 25 degrees C since then, the heart and the cardiac cells were hypertrophied, total capillary density increased and the capillary domain areas were reduced along the capillary path from the arteriolar to venular capillary portions. The number of the venular capillary portions showed no significant change but the arteriolar and intermediate capillary portions significantly increased. All these changes suggest that the cardiac capillary network was better developed in the cold-reared rats than in control rats. In the cold-adapted rats the hypertrophic changes in cardiac cells are thus accompanied by improvements in the oxygen delivery capacity. This adaptation provides a basis for the maintenance of increased thermogenesis in many organs. The changes cannot be established by several weeks exposure to low temperature, but only after rats have been bred in a cold room for generations.

Adaptation, Physiological↗

Effects of treadmill training on the arteriolar and venular portions of capillary in soleus muscle of young and middle-aged rats.

The effects of a 6-week programme of endurance training on soleus muscle capillarity were examined, in terms particularly of the proportions of arteriolar and venular capillaries and their capillary domain area, in young (3-week-old) and middle-aged (54-week-old) Wistar rats. Exercise protocols for the young training group were: 10-22.5 m min-1 60 min day-1 for 6 days a week, with a gradient of 7 degrees during the final 2 weeks; for the middle-aged training group, the protocols were: 10-20 m min-1. 50 min day-1 for 6 days a week. In both young and middle-aged training groups, the density of arteriolar capillaries was significantly increased (P < 0.05), but that of venular and intermediate capillaries was decreased slightly. The proportion of arteriolar capillaries therefore was significantly (P < 0.05) increased, from 63.9 to 73.1% in young rats and from 33.0 to 48.4%, in middle-aged rats after training. The increase in the proportion of arteriolar capillaries is an advantageous adaptation to exercise-induced increases in oxygen demand. In both young and middle-aged rats, capillary domain area and Krogh's tissue cylinder radii in all capillary portions decreased after training. These results suggest that adaptive changes in oxygen transport system, identified as an increase in the arteriolar capillary and a reduction in diffusion distance for oxygen, were observed in middle-aged as well as in young rats. However, capillary angiogenesis induced by exercise appeared to be greater in young than in middle-aged rats.

Aging↗

Remodeling of capillary network in left ventricular subendocardial tissues induced by intravenous vasopressin administration.

OBJECTIVE: The question of whether the coronary vasospasm induced by intravenous administration of vasopressin produces any remodeling of the capillary network in the left ventricle was investigated. To this end, cardiac tissues obtained from vasopressin-injected rats were stained to allow capillary counting and for basic fibroblast growth factor (bFGF). METHODS: Nine male Donryu rats were divided into three groups that received, respectively, 0.25 ml of saline containing 0, 0.5, or 1.0 U/kg vasopressin injected into the tail vein once daily for 4 days. Rats were killed 30 days after the last injection. Two additional rats each received a single intravenous injection of 1.0 U/kg vasopressin and were killed 24 hours later. The left ventricles were removed and 16- or 10-micron frozen sections were cut for differential staining and distribution of bFGF, respectively. Differential staining was used to classify the capillary portions, and bFGF was identified by immunohistological staining. RESULTS: Compared with the control group, total capillary density was increased in both vasopressin-treated groups, capillary to myocyte ratio was increased, and the capillary domain areas decreased in the three capillary portions. Arteriolar and intermediate capillary portions increased, while the venular capillary portion decreased. In rats killed 24 hours after vasopressin injection, a considerable amount of bFGF could be demonstrated immunohistochemically in the ventricular tissues, and the punctate distribution of bFGF was still found in rats killed 30 days after treatment. CONCLUSIONS: A remodeling of capillary network which would increase the oxygen transport capacity to cardiac tissues was produced in left ventricular tissues by intravenous injection of vasopressin. bFGF located around capillaries and in the interstitial space may have been involved in the capillary remodeling.

Animals↗

Potentiation by estramustine of the cytotoxic effect of vinblastine and doxorubicin in prostatic tumor cells.

The effects of combining estramustine (EM) with vinblastine (VLB) or doxorubicin (DOX) on cellular uptake, cellular retention and cell survival were investigated in Dunning hormone-insensitive rat prostate AT-1 tumor cells and DU-145 human prostatic tumor cells. Accumulation of VLB and DOX by AT-1 cells was less than one-half of that in DU-145 cells. Inclusion of EM or estromustine considerably increased uptake of both VLB and DOX in AT-1 cells but not in DU-145 cells. Verapamil and tamoxifen also potentiated VLB uptake in AT-1 cells. A combination of VLB and EM resulted in a considerable synergistic effect on both cytotoxicity and cellular retention of VLB. The presence of P-glycoprotein (Pgp) in AT-1 cells could be demonstrated by both Western blots and immunocytochemical detection. Photoaffinity labeling of Pgp by [3H]-azidopine was clearly inhibited by VLB, verapamil and EM. Our data strongly support the argument for a combination of EM with not only VLB but also DOX to improve the therapeutic index in patients with prostate cancer.

Animals↗

Binding of vinblastine and estramustine to isolated plasma membrane fractions from human prostate and prostatic tumors.

The binding of vinblastine (VLB) and estramustine (EM) to plasma membranes isolated from human prostate, prostatic tumors as well as from Dunning rat prostatic AT-1 tumors was studied. In addition, the uptake of these drugs in AT-1 tumor cells in culture was examined. Binding of VLB was six-fold lower than that of EM in membrane preparations from all three sources. The uptake of VLB in the intact AT-1 cells was nearly five-fold lower than that of EM. At concentrations comparable to those achieved clinically the binding of EM was 100-fold higher than that of VLB. The data suggest that, owing to a very high membrane concentration of EM relative to that of VLB, the active efflux VLB in drug resistant cells would be impeded. This in turn would lead to a higher accumulation of VLB in cells that actively transport cytotoxic drugs.

Animals↗

Photoaffinity labeling of peripheral benzodiazepine receptors in R-3327 Dunning prostatic tumors.

Photoaffinity labeling of peripheral benzodiazepine receptors (PBZr) in mitochondrial and microsomal fractions from AT-1, H, and G Dunning R-3327 tumor sublines was performed using the photoaffinity ligand 3H-PK 14105. Subsequent sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis (PAGE) revealed specific labeling of a 17 kDa protein in the microsomal fractions from these tumors. In the mitochondrial fractions, however, two bands with the apparent molecular mass of 17 and 18 kDa in AT-1 and H tumors were identified, whereas only the 17 kDa band was present in G tumors. Using another ligand, 3H-flunitrazepam, to photoaffinity label PBZr, proteins with molecular masses of 17, 30, 42, and 48 kDa were identified. These data suggest the possibility of different subclasses of PBZrs in Dunning prostatic tumors.

Affinity Labels↗

Elevated concentrations of antiestrogen binding sites in membrane fractions of human ovarian tumors.

The density and affinity of tamoxifen (TAM) binding sites in isolated plasma membrane fractions from human ovarian tissue and ovarian tumors was measured. TAM binding in both membrane preparations was specific, saturable, and had a high affinity (KD < 1 nM). The density of TAM binding sites in the tumors was at least three times higher than that in the normal ovaries, whereas the affinity of TAM binding sites in the tumors was lower than in normal ovaries. The relatively large number of TAM binding sites that are distinct from estrogen receptors in ovarian tumors suggest that TAM alone and in combination with other chemotherapy could be used with advantage in ovarian cancer.

Adult↗

Needle-knife sphincterotomy in a tertiary referral center: efficacy and complications.

BACKGROUND: The use of needle-knife sphincterotomy as a method of precut sphincterotomy has been criticized as potentially unsafe. Despite this, a number of tertiary referral centers have reported their successful use of this technique to increase the rate of common bile duct cannulation. METHODS: We assessed the safety and efficacy of needle-knife sphincterotomy in 72 consecutive patients in whom attempts at standard common bile duct cannulation were unsuccessful. Bile duct diameters were correlated to the complication rate. RESULTS: Cannulation of the common bile duct was successful immediately after needle-knife sphincterotomy in 50 patients (67%), and was successful in 17 of the 20 patients who underwent repeat ERCP, for a total cannulation rate of 93%. Eight patients (11%) experienced complications. Retroduodenal perforation during guide wire cannulation attempts and bleeding occurred as frequently as pancreatitis. Small duct size was a risk factor for complications. There was no procedure-related mortality, and all complications were managed medically. CONCLUSIONS: Needle-knife sphincterotomy was effective in facilitating cannulation in patients in whom standard cannulation attempts failed. Limiting guide wire manipulation of the fresh sphincterotomy site and excluding patients with small duct size may further reduce the complication rate.

Adult↗

Inhibition of contractile responses of human myometrium and intramyometrial arteries by potassium channel openers.

OBJECTIVES: The effects of cromakalim and pinacidil on the contractile activity of the isolated human myometrium and intramyometrial arteries were studied. MATERIAL AND METHOD: Myometrial strips and pieces of uterine arteries were obtained from women undergoing hysterectomy. Contractions were recorded under isometric conditions. RESULTS: Both compounds (10(-9) M-5 x 10(-6) M) inhibited the spontaneous activity of the myometrium and vasopressin induced contractions of myometrium and intramyometrial arteries. There was no statistically significant difference in the responses of both tissues to cromakalim or pinacidil. Both compounds reduced responses of myometrium and intramyometrial arteries to low concentration of K+ (< 40 mM) but did not decrease contractions induced by 40 mM and 80 mM. CONCLUSION: The combined effect on the uterus and intrauterine vasculature would suggest a potential in the use of cromakalim or pinacidil for the treatment of dysmenorrhea.

Adult↗

The urokinase inhibitor p-aminobenzamidine inhibits growth of a human prostate tumor in SCID mice.

Malignant cells possess a high degree of proteolytic activity in which the plasminogen activator system plays an important role. An increased expression of urokinase type plasminogen activator (uPA) is of significance for degradation of the extracellular tumor matrix, facilitating invasiveness and growth. Inhibition of the active site of uPA makes it possible to evaluate the significance of uPA in tumor growth. We report here experiments on a uPA-producing human prostate xenograft (DU 145) using a competitive inhibitor of uPA, p-aminobenzamidine. In vitro experiments with DU 145 cells showed that p-aminobenzamidine caused a dose-dependent inhibition of uPA activity. DU 145 cells were inoculated s.c. in SCID mice and, once tumors were established, treatment with p-aminobenzamidine added to drinking water was started and lasted for 23 days. Mice receiving 250 mg/kg/day of p-aminobenzamidine showed a clear decrease in tumor-growth rate compared to the non-treated mice, resulting in 64% lower final tumor weight. In addition, uPA-antigen levels in the membrane fractions of DU 145 tumors from p-aminobenzamidine-treated mice were found to be decreased by 59%. We also show that p-aminobenzamidine has an anti-proliferative effect in cell culture at low cell number, correlating with a dose-dependent decrease in uPA production. In conclusion, we show that a low-molecular-weight uPA-inhibitor, p-aminobenzamidine, has a growth-inhibitory effect on a solid uPA-producing tumor.

Adenocarcinoma↗

Modulation of peripheral benzodiazepine receptor density by testosterone in Dunning G prostatic adenocarcinoma.

Effect of orchiectomy on peripheral benzodiazepine receptors (PBZr) density in hormone sensitive, poorly differentiated Dunning G rat prostatic tumors were studied. A significant increase in PBZr density (1.4-fold) was observed in both mitochondrial fractions (m-fractions) and microsomal fractions (p-fractions) of tumors from orchiectomized rats as compared to tumors from sham operated controls. Substitution with testosterone in orchiectomized rats repressed the PBZr density in both m- and p-fractions to that of the control animals. The data strongly suggest a regulatory role of testosterone on the PBZr density in these hormone sensitive prostatic tumors.

Adenocarcinoma↗

Phase contrast microscopic evaluation of placental pathology in premature gestation.

Numerous representative samples taken from forty placentas immediately after delivery from mothers associated with prematurity (i.e. less than 38 weeks), were semiquantitatively studied by phase contrast microscopy. Twenty placentas delivered from mothers without any antenatal complication served as control. Hypoplasia of the syncytium, stromal edema, ischaemia were prominent findings on phase contrast microscopy in the study group. Increased basement membrane thickening and high villous edema scores observed on light microscopy were statistically significant in prematurity as compared to controls. Observations by phase contrast and light microscopy were found complementary to each other. Phase contrast microscopy provided quicker results without disadvantage of fixation artefact and was found distinctly superior over the conventional histological methods.

Case-Control Studies↗

Release of intracellular calcium and stimulation of cell growth by ATP and histamine in human ovarian cancer cells (SKOV-3).

The effects of ATP and histamine on cell proliferation and intracellular calcium concentrations ([Ca2+]i) were examined in the human ovarian cancer cell line SKOV-3. Micromolar concentrations of ATP induced a biphasic increase in [Ca2+]i representing a rapid rise to a peak level followed by a smaller but more sustained phase. When influx of extracellular calcium was blocked by calcium chelation to EGTA, the ATP-stimulated rise in [Ca2+]i was rapid and only monophasic. Histamine, in contrast to ATP, caused only a monophasic rise in [Ca2+]i both in the presence and absence of external calcium. The histaminergic H1 receptor antagonist pyrilamine, but not the H2 receptor antagonist cimetidine, totally blocked rises in [Ca2+]i caused by histamine. Fetal calf serum (FCS) induced a slow and monophasic increase in [Ca2+]i in these cells, distinctly different from rises in [Ca2+]i caused by ATP and histamine. Inclusion of low micromolar concentrations of ATP in the growth medium stimulated proliferation of these cells, while higher concentrations (100 microM-1 mM) significantly decreased cellular proliferation. Histamine, in micromolar concentrations, also stimulated cell proliferation. From these results it was concluded that the release of intracellularly bound Ca2+ following receptor stimulation is sufficient to induce cellular proliferation in SKOV-3 cells.

Adenosine Triphosphate↗