Search PubMed⌕ Search

Biomedical subjects

C A Sninsky

Publications and source records attributed to C A Sninsky.

At least 37 records · Page 2Linked to original sources
PubMed1995

The impact of polyamine analogues on the blood pressure of normotensive and hypertensive rats.

The impact of the antineoplastic polyamine analogues N1N14-diethylhomospermine (DEHSPM) and N1N11-diethylnorspermine (DENSPM) on the blood pressure and heart rate of normotensive and hypertensive rats are described. DEHSPM was administered to both normotensive and spontaneously hypertensive rats (SHR), while the DENSPM analogue was given only to the normotensive animals. The intravenous administration of DEHSPM at doses of 5 or 10 mg/kg resulted in a profound and long-lasting drop in the test animals' blood pressure, with no appreciable change in their heart rate. This was true for both the normotensive and the hypertensive animals. When administered at equivalent molar dosages, DENSPM was one fifth as effective as DEHSPM at reducing blood pressure. The impact of NG-nitro-L-arginine-methyl ester (L-NAME) and L-arginine on the analogues' activity is consistent with the involvement of nitric oxide.

Amines↗
PubMed1994

Erythromycin enhances gastric emptying in patients with gastroparesis after vagotomy and antrectomy.

We studied the effect of erythromycin on gastric emptying in nine patients with gastroparesis following truncal vagotomy and antrectomy, and assessed their clinical response to chronic oral erythromycin. Gastric emptying was evaluated using a solid-phase radio-labeled meal. Patients were studied after erythromycin 200 mg intravenously (N = 9) and after an oral suspension of erythromycin 200 mg (N = 7) each given 15 min after ingestion of the meal. Three parameters of gastric emptying were analyzed: half-emptying time (T1/2), area under the curve, and percent gastric residual at 2 hr. Nine patients were subsequently placed on oral suspension erythromycin 150 mg three times a day before meals (range 125-250 mg three times a day) and symptoms of nausea, vomiting, postprandial fullness, and abdominal pain were assessed before and after erythromycin. Intravenous erythromycin markedly accelerated the gastric emptying (all three parameters studied) of solids (P < 0.01) in seven of nine patients with postsurgical gastroparesis [baseline T1/2 154 +/- 15 min; after intravenous erythromycin, T1/2 56 +/- 17 min (mean +/- SEM)]. Oral erythromycin enhanced (P < 0.05) the gastric emptying rate (T1/2, area under the curve) in five of seven patients (baseline T1/2 146 +/- 16 min; after oral erythromycin, T1/2 87 +/- 20 min). Of the nine patients who were placed on oral maintenance erythromycin, three showed clinical improvement after two weeks. In summary, erythromycin significantly enhances gastric emptying in many patients with vagotomy and antrectomy-induced gastroparesis; however, only a small subset of patients respond clinically to chronic oral erythromycin.

Administration, Oral↗
PubMed1993

Ketorolac prevents postoperative small intestinal ileus in rats.

The effect of ketorolac, a parenterally administered, nonsteroidal anti-inflammatory drug, was examined in a rat model of postoperative ileus. Small intestinal transit was measured by calculating the geometric center (GC) of distribution of 51CrO4. Laparotomy significantly delayed transit (GC: 2.2 +/- 0.2 after laparotomy versus 5.6 +/- 0.5 for unoperated controls, p < 0.01). The administration of ketorolac (1 mg/kg) improved the GC to 5.2 +/- 0.2 (p < 0.01), indicating normal intestinal transit after surgery in ketorolac-treated animals. Small intestinal myoelectric activity was recorded in rats with implanted electrodes. Animals treated with saline 2 hours postoperatively did not show return of the migrating myoelectric complex (MMC) in 183 +/- 25 minutes. In contrast, rats receiving ketorolac postoperatively had return of MMC activity in 59 +/- 18 minutes (p < 0.01). Preoperative ketorolac treatment reduced the duration of MMC inhibition after surgery from 197 +/- 55 minutes to 13 +/- 5 minutes (p < 0.05) when compared with saline. In summary, ketorolac hastens the return of MMC activity when given postoperatively. When ketorolac is administered preoperatively, it completely prevents the delay in intestinal transit and the inhibition of myoelectric activity seen in postoperative ileus. We concluded that ketorolac may be of benefit in the prevention and treatment of postoperative ileus.

Animals↗
PubMed1993

Assessment of proteinuria and neuropathy in the nonimmunosuppressed BB diabetic rat after abdominal intratesticular islet transplantation.

Only limited studies are available that assess diabetic complications following islet cell transplantation. Our objectives were to quantitate urine total protein, sural nerve morphometry, and sexual function in the diabetic BB/WOR male rat following islet cell transplantation into the abdominal testis. Success of islet cell transplantation was determined by nonfasting, morning, twice-weekly serum glucose and 12-hr fasting glucose, total glycosylated hemoglobin, and HbA1c after six months of diabetes and prior to death. Results showed that 9 of 16 rats were transplanted successfully for a period of at least six months. Pretransplant glucose was 21.9 +/- 4.67 (SD) mM/L and posttransplant glucose was 6.44 +/- 72 mM/L. The 12-hr fasting glucose ranged from 4.61 to 9.28 mM/L in animals prior to death, and glycosylated hemoglobins were not different from controls. Total urinary protein was significantly (P < 0.01) less than untreated diabetic rats (5.66 +/- 1.96 vs. 16.6 +/- 3.7 mg/24 hr) and not different from controls. Penile reflexes and serum testosterone remained normal in islet cell-transplanted animals. Sural nerve morphometry was normal, with 29.2% fewer abnormalities (paranodal swelling, paranodal demyelination, myelin wrinkling, Wallerian degeneration, and segmental demyelination) than untreated diabetic BB/WOR rats. We conclude that abdominal, intratesticular islet transplantation normalizes fasting blood glucose and glycosylated hemoglobin. In addition, the improvement in metabolic control at six months of diabetes was associated with normal total urinary protein, sural nerve morphometry, and sexual function.

Animals↗
PubMed1993

Effect of insulin on the altered thyroid function and adrenergic responsiveness in the diabetic rat.

We have previously reported the tail skin temperature response to isoproterenol as being significantly attenuated in male rats 4 weeks after the induction of diabetes with streptozotocin. The current study evaluated the time course of this altered adrenergic responsiveness and the role of thyroid hormone and insulin treatment in the tail skin temperature response. In the first study, the tail skin temperature response to isoproterenol was monitored weekly, for 6 weeks. The tail skin temperature response was similar in control and diabetic animals after 1 week of streptozotocin treatment. However, after 2, 4, 5, and 6 weeks of diabetes the tail skin temperature response was significantly reduced. Total T3, T4, and free T4 concentrations were also significantly reduced in these diabetic animals. In a second study, the effects of graded doses of insulin treatment on thyroid hormone levels was assessed. The reduced thyroid hormone concentrations observed in untreated streptozotocin-diabetic rats were restored towards control levels in animals receiving the lowest dose of insulin (1 U/day), whereas higher doses of insulin were required to more closely restore euglycemia and lower glycated hemoglobin. A subsequent study, utilizing a 1-U/day dose of insulin, resulted in a normalization of the tail skin temperature response to isoproterenol, during 8 weeks of treatment in the treated diabetic rat. In a final study utilizing the spontaneous BB diabetic rat maintained on daily insulin treatment, no differences in the tail skin temperature response or thyroid hormone levels were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Human gastric myoelectric activity and gastric emptying following gastric surgery and with pacing.

Postoperative gastric myoelectric activity, gastric emptying, and clinical course were correlated in 17 patients at high risk of developing gastroparesis after gastric surgery. In addition, an attempt was made to pace the stomach with an electrical stimulus and determine the effect of pacing on early postoperative gastric emptying. Gastric dysrhythmias (bradygastria, slow wave frequency < 2 cycles/min; tachygastria, slow wave frequency > 4 cycles/min) persisted beyond the first postoperative day in 6 patients (35%). Delayed gastric emptying was identified by a radionuclide meal in 15 patients (88%), but symptoms of gastroparesis developed in only 6 of 15 (40%). Patients with postoperative gastroparesis had more frequent dysrhythmias than asymptomatic patients (67% vs. 18%), but these differences were not significant, although we cannot exclude a type II statistical error. Gastric rhythm was entrained in 10 of 16 patients (63%). Pacing increased the gastric slow wave frequency (3.1 vs. 4.1 cycles/min; P < 0.01) but did not improve gastric emptying (gastric retention at 60 minutes, 86% +/- 6% for control and 90% +/- 2% for paced). In conclusion, gastric dysrhythmias do not appear to play a major role in the development of postsurgical gastroparesis. Although gastric rhythm could be entrained in the majority of patients, pacing did not improve gastric emptying overall.

Adult↗
PubMed1992

Neuropeptide Y release from the paraventricular nucleus increases in association with hyperphagia in streptozotocin-induced diabetic rats.

We tested the hypothesis that the hyperphagia observed in streptozotocin (STZ)-induced diabetic rats is due to increased release of neuropeptide Y (NPY) in the paraventricular nucleus (PVN) of the hypothalamus. In the first experiment, male rats were injected with STZ or vehicle (control) via the tail vein and 18-20 days later, NPY levels in seven hypothalamic sites and release in vitro from selected hypothalamic sites were evaluated. The results showed that in association with STZ-produced marked hyperglycemia and hyperphagia, NPY concentrations were increased in four hypothalamic sites, including the PVN. Evaluation of NPY release in vitro showed that both basal and KCl-induced release was significantly higher from the micro-dissected PVN of STZ-treated than control rats. A similar augmentation in the NPY efflux in vitro was detected from the median eminence arcuate nucleus, but not from the neighboring ventromedial nucleus of STZ-treated rats. In the second experiment, rats were treated with STZ or vehicle and received permanent push-pull cannula (PPC) in the PVN for evaluation of NPY release in vivo 18-21 days after STZ treatment. The results showed that mean NPY levels in the perfusates collected from the PVN of diabetic rats were significantly higher as compared to control rats. Since NPY is the most potent naturally occurring orexigenic signal and the PVN is an important initial site of NPY action in the stimulatory pathway regulating feeding, our findings of augmented PVN NPY release in vivo and in vitro are in accord with the hypothesis that increased NPY secretion in the PVN may be responsible for hyperphagia in diabetic rats.

Animals↗
PubMed1991

Oral mesalamine (Asacol) for mildly to moderately active ulcerative colitis. A multicenter study.

OBJECTIVE: To evaluate the efficacy and safety of a pH-sensitive, polymer-coated oral preparation of mesalamine in patients with mildly to moderately active ulcerative colitis. DESIGN: A multicenter, double-blind, placebo-controlled randomized trial. SETTING: Five university-based medical centers, one inflammatory bowel disease center, and three private practice sites. PATIENTS: A total of 158 patients with newly or previously diagnosed active ulcerative colitis. INTERVENTION: A pH-sensitive, polymer-coated oral preparation of mesalamine (5-aminosalicylic acid) was used at 1.6 and 2.4 g/d for 6 weeks. MEASUREMENTS: Efficacy was measured by scores for stool frequency, rectal bleeding, patient's functional assessment, sigmoidoscopic findings, and physician's global assessment. Stringent criteria for disease activity were established prospectively. RESULTS: The analysis of protocol-compliant patients showed a significant improvement at 3 weeks in patients taking 2.4 g/d of mesalamine compared with patients taking placebo (32% versus 9%; P = 0.003). At 6 weeks, both the 1.6 g/d (43%) and 2.4 g/d (49%) doses were significantly superior to placebo (23%) (P = 0.03 and P = 0.003, respectively). In addition, more patients worsened in the placebo group compared with the 2.4 g/d group (50% versus 19%; P = 0.003); however, there was no statistically significant difference in worsening between the 1.6 g/d mesalamine group and the placebo group. The oral mesalamine tablet was well tolerated, and no clinically significant changes were observed in hematologic, hepatic, or renal laboratory profiles. CONCLUSION: Colon-targeted oral mesalamine at 2.4 g/d is effective therapy for mildly to moderately active ulcerative colitis. It is well tolerated and should provide a viable therapeutic alternative to sulfasalazine.

Administration, Oral↗
PubMed1991

Erythromycin enhances delayed gastric emptying in dogs after Roux-Y antrectomy.

Delayed gastric emptying occurs in up to 50% of patients after truncal vagotomy and Roux-Y antrectomy and is often resistant to nonsurgical therapy. This study evaluates the effect of erythromycin, metoclopramide, and motilin on delayed gastric emptying in four dogs after Roux-Y antrectomy. Solid food gastric emptying was measured using a radionuclide technique. Study groups were: (1) saline control; (2) erythromycin 1 mg/kg intravenously over 1 hour; (3) erythromycin 3 mg/kg by mouth 45 minutes prior to feeding; (4) metoclopramide 0.6 mg/kg intravenously over 1 hour; and (5) motilin 500 ng/kg intravenously over 1 hour. After Roux-Y antrectomy, saline control dogs had 73% +/- 5% (SEM) gastric retention at 2 hours. After intravenous and oral erythromycin, gastric emptying improved at 2 hours to 27% +/- 6% and 39% +/- 5% (p less than 0.01 compared with control). Erythromycin intravenously and by mouth improved gastric emptying compared with metoclopramide (64% +/- 8%, p less than 0.05). Motilin enhanced gastric emptying to a similar degree as erythromycin, with a 2-hour gastric retention of 37% +/- 4% (NS). Erythromycin improved gastric emptying in dogs with severe Roux-Y gastroparesis and may have clinical application.

Administration, Oral↗
PubMed1991

Erythromycin acts through a cholinergic pathway to improve canine-delayed gastric emptying following vagotomy and Roux-Y antrectomy.

We have demonstrated that erythromycin improves gastric emptying in dogs following truncal vagotomy and Roux-en-Y antrectomy (VRYA). To explore its mechanism of action we studied gastric emptying and myoelectric activity in a canine Roux model and administered atropine simultaneously with erythromycin. Tachyphylaxis was evaluated following short-term administration. Four dogs with delayed gastric emptying following VRYA were studied. Radionuclide solid gastric emptying was measured, with simultaneous myoelectric recordings obtained from the duodenum and Roux limb. Study groups were: (1) saline control (VRYA dogs); (2) erythromycin 1 mg/kg iv over 1 hr; (3) erythromycin 3 mg/kg po tid for 1 week, with repeat studies using erythromycin 1 mg/kg iv over 1 hr; and (4) atropine 0.5 mg/kg iv bolus, followed by a 1-hr infusion of atropine 0.05 mg/kg and erythromycin 1 mg/kg. Control Roux animals had severe gastric retention (73 +/- 5% at 2 hr, compared to 27 +/- 6% following iv erythromycin (P less than 0.01). Clustered spike bursts were observed in the Roux limb following erythromycin. Atropine abolished the gastrokinetic response and suppressed the myoelectric response to erythromycin (81 +/- 3% retention at 2 hr, P less than 0.01 compared to erythromycin alone). The response to erythromycin was unchanged after 1 week of tid administration (40 +/- 14% retention at 2 hr postprandial, P = NS). Erythromycin improves gastric emptying in VRYA dogs via a cholinergic pathway and does not exhibit tachyphylaxis following short-term administration.

Anastomosis, Roux-en-Y↗
PubMed1991

Evidence against impaired brain microtubule protein polymerization at high glucose concentrations or during diabetes mellitus.

Previous studies suggest that brain microtubule protein exposed to high glucose levels or isolated from diabetic rats can become glucosylated and that this impairs GTP-induced microtubule polymerization. We set out to extend that investigation to define the mechanistic basis for inhibition of microtubule assembly during diabetes or on incubation at high glucose levels. Rat and bovine brain microtubule protein was purified by cycles of polymerization/depolymerization. When microtubules were incubated for 1 h in either buffer or buffer containing glucose (up to 165 mM), there was no difference in polymerization, a finding contrary to the earlier study. Other rats were injected with vehicle or streptozotocin (90 mg/kg) to induce diabetes as evidenced by serum glucose in excess of 300 mg%, and at 4 weeks, brain microtubule protein was isolated by the polymerization cycling method. Again, there was no difference in the amount or purity of isolated microtubule protein between control or diabetic rats. We also observed no increase in microtubule glucosylation, and GTP-induced polymerization in vitro was indistinguishable for protein derived from brains of normal rats and rats with diabetes as measured by turbidity or electron microscopy. Our results suggest that in vitro incubation with glucose or in vivo elevation of glucose during diabetes fails to impair microtubule polymerization, pointing to other mechanisms for the neuropathy associated with diabetes.

Animals↗
PubMed1991

Antiperistaltic and isoperistaltic intussusception associated with abnormal motility after Roux-en-Y gastric bypass: a case report.

Antiperistaltic and recurrent intussusceptions are extremely rare in the adult. We report a patient with both. The patient developed an antiperistaltic intussusception distal to her Roux enteroenterostomy years after a Roux-en-Y gastric bypass for morbid obesity. The diagnosis was made preoperatively with gastrointestinal contrast radiography and ultrasonography. At surgery, the intussusception was reduced, and 12 inches of nonviable bowel was resected, with a functional end-to-end anastomosis. An isoperistaltic intussusception occurred in the early postoperative period just distal to the anastomosis. Manometric evaluation of the Roux limb after the second operation showed altered gastrointestinal motility, consisting of orad-propagated and aboard-propagated migrating motor complexes, minimal phase 2 activity, and lack of conversion to the fed pattern with a liquid meal. Although manometry was not performed before the development of the intussusception, our findings are consistent with the hypothesis that altered intestinal motility may contribute to the development of intussusception.

Adult↗
PubMed1990

Gastric dysrhythmias following pylorus-preserving pancreaticoduodenectomy. Possible mechanism for early delayed gastric emptying.

Transient delayed gastric emptying is reported as a frequent complication following pancreas-preserving pancreaticoduodenectomy (PPW). We placed serosal electrodes on the stomach of a patient undergoing PPW. Myoelectric recordings were obtained postoperatively and correlated with simultaneous radionuclide liquid gastric emptying studies. The patient developed early postoperative gastric atony, associated with frequent gastric dysrhythmias. These dysrhythmias may have been exacerbated by a perihepatic abscess. The gastric dysrhythmias correlated with alterations in liquid gastric emptying. Gastric dysrhythmias may be a mechanism for gastric dysfunction in the early postoperative period.

Adenocarcinoma↗
PubMed1990

Neurofilament immunoreactivity in myenteric neurons differs from that found in the central nervous system.

Neurofilaments are 10-nm diameter protein fibers found within neurons and are composed predominantly of a triplet of polypeptides usually referred to as low-, medium-, and high-molecular-weight subunits. We describe the results of a study of myenteric plexus neurons using a panel of neurofilament triplet protein antibodies and indirect immunofluorescence techniques. Polyclonal antibodies to each of the three neurofilament subunits reliably stained myenteric neurons and their processes, indicating the presence of all three proteins in these cells. However, several well-characterized monoclonal antibodies to epitopes on high- and medium-molecular-weight subunits showed immunoreactivity in brain tissue but not in myenteric neurons and their processes. Some of the antibodies that do not stain recognize only phosphorylated epitopes, indicating that the level of neurofilament phosphorylation is very low in enteric neurons. Other antibodies that are not thought to be sensitive to the level of neurofilament phosphorylation show reduced or no staining of enteric neurons, suggesting the presence of immunologically distinct neurofilaments in these cells. These results suggest the presence of modified neurofilament structures in enteric neurons, possibly reflecting their unique mechanical character within the moving intestinal wall.

Animals↗
PubMed1990

Neuropeptide-Y concentration in microdissected hypothalamic regions and in vitro release from the medial basal hypothalamus-preoptic area of streptozotocin-diabetic rats with and without insulin substitution therapy.

Experimental diabetes adversely affects hypothalamic control of gonadotropin secretion and sex behavior and induces hyperphagia accompanied by severe body weight loss. Neuropeptide-Y (NPY) stimulates pituitary gonadotropin release, inhibits sexual behavior, and stimulates robust feeding in rats by acting at different sites in the hypothalamus. Therefore, we tested the hypothesis that altered hypothalamic NPY neurosecretion may mediate the constellation of effects observed in streptozotocin-induced diabetic (STZ-D) rats. Adult male rats were made diabetic by a single injection of STZ (50 mg/kg). Five months later, in vitro NPY release from the hypothalamic fragment encompassing the medial basal hypothalamus and preoptic area and NPY concentrations in seven hypothalamic sites were assessed. Basal NPY release was not significantly changed after STZ treatment. However, in response to a 30-min pulse of KCl (45 mM), NPY release from the medial basal hypothalamus-preoptic area of STZ-D rats was significantly increased compared to that in age-matched controls. In the STZ-D rats, NPY concentrations in six of the seven microdissected nuclei, including those mediating control of pituitary gonadotropin, sexual, and feeding behaviors, were increased compared to control values. In an additional study similar increments in NPY concentrations in the hypothalamic sites were observed 6 months after STZ treatment. The effects of insulin on NPY levels in microdissected hypothalamic sites in STZ-treated and BB diabetic rats was next assessed. One group of rats was treated with STZ, and the other group of rats was additionally treated with insulin (6 U/kg.day) for 3 months after development of diabetes with STZ. Again, STZ treatment alone, even for 3 months, increased NPY levels in all seven nuclei, including the suprachiasmatic nuclei. Insulin therapy completely prevented the STZ-induced increments in NPY levels in all hypothalamic sites, and the blood glucose level was 233 +/- 22 mg/dl in insulin-treated STZ-D rats and 496 +/- 6 mg/dl in untreated STZ-D rats. Similarly, NPY concentrations in five of the seven nuclei were unchanged in spontaneously diabetic BB rats (blood glucose, 435 +/- 67 mg/dl) maintained on insulin (5-8 U/kg.day). These results demonstrate that STZ-D rats have a widespread increase in NPY levels in hypothalamic sites, and there is an increase in the evoked release of NPY from the hypothalamus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Effect of berberine on myoelectric activity and transit of the small intestine in rats.

The motility of the small intestine in unanesthetized rats receiving berberine sulfate (0.2, 2.0, and 20.0 mg/kg i.p.) was investigated. Motility was determined by two methods: myoelectric activity was monitored with indwelling bipolar electrodes, and intestinal transit was measured by the movement of radiochromium (Na51CrO4). The 20.0-mg/kg dose caused a marked inhibition of spike activity for 21.8 +/- 7.0 min and disrupted activity fronts of the migrating myoelectric complex for 212.3 min. Berberine, 2.0 mg/kg i.p., disrupted migrating myoelectric complexes for 64.6 min but spike inhibition was not observed. Transit of the small intestine was significantly (p less than 0.001) delayed at 15 and 100 min after the highest dose of berberine. Naloxone blocked the spike inhibition noted with 20.0 mg/kg of berberine but failed to improve transit. Phentolamine blocked spike inhibition and was associated with a significantly earlier return of activity fronts of the migrating myoelectric complex. Animals pretreated with this antagonist tended toward a higher geometric center in transit studies than those injected with berberine alone. Berberine was also administered by various routes (intraperitoneal injection, intravenous injection, orogastric gavage, and intraluminal injection). An intraperitoneal injection was 10-fold more potent than an intravenous injection. Orogastric gavage and intraluminal administration of berberine did not alter intestinal motility. In summary, berberine sulfate significantly inhibits myoelectric activity and transit of the small intestine. This appears to be partially mediated by opioid and alpha-adrenergic receptors. The antidiarrheal properties of berberine may be mediated, at least in part, by its ability to delay small intestinal transit.

Administration, Oral↗