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M Niehoff

Publications and source records attributed to M Niehoff.

17 recordsLinked to original sources
PubMed2004

Measurement of DNA damage after acute exposure to pulsed-wave 2450 MHz microwaves in rat brain cells by two alkaline comet assay methods.

PURPOSE: To investigate the effect of 2450 MHz pulsed-wave microwaves on the induction of DNA damage in brain cells of exposed rats and to discover whether proteinase K is needed to detect DNA damage in the brain cells of rats exposed to 2450 MHz microwaves. MATERIALS AND METHODS: Sprague-Dawley rats were exposed to 2450 MHz pulsed-wave microwaves and sacrificed 4 h after a 2-h exposure. Rats irradiated whole-body with 1 Gy (137)Cs were included as positive controls. DNA damage was assayed by two variants of the alkaline comet assay on separate aliquots of the same cell preparation. RESULTS: Significant DNA damage was observed in the rat brain cells of rats exposed to gamma-rays using both versions of the alkaline comet assay independent of the presence or absence of proteinase K. However, neither version of the assay could detect any difference in comet length and/or normalized comet moment between sham- and 2450 MHz pulsed-wave microwave-exposed rats, regardless of the inclusion or omission of proteinase K in the comet assay. CONCLUSIONS: No DNA damage in brain cells was detected following exposure of rats to 2450 MHz microwaves pulsed-wave at a specific absorption rate of 1.2 W kg(-1) regardless of whether or not proteinase K was included in the assay. Thus, the results support the conclusion that low-level 2450 MHz pulsed-wave microwave exposures do not induce DNA damage detectable by the alkaline comet assay.

Animals↗
PubMed1999

Laparoscopic v laparoscopy-assisted donor nephrectomy in the porcine model.

PURPOSE: Laparoscopic donor nephrectomy is an established procedure in the porcine model. We sought to compare intraoperative variables between live laparoscopic (LAP) and laparoscopy-assisted (LAP-A) donor nephrectomy. MATERIALS AND METHODS: Eight domestic pigs underwent either traditional laparoscopic donor nephrectomy (N = 4) or laparoscopy-assisted donor nephrectomy (N = 4) using the Pneumosleeve followed by conventional heterotopic autotransplantation. RESULTS: No significant differences were noted between the groups with regard to vessel length, ureteral length, or postoperative urine output. The operating room time was 108+/-12 minutes in the LAP group v 75.8+/-10.3 minutes in the LAP-A group (P = 0.0065). Although the difference was not statistically significant, warm ischemic time, tended to be lower in the LAP-A than the LAP group: 70+/-3.0 seconds v 135+/-57 seconds, respectively (P = 0.059). Graft survival was identical in the two groups. CONCLUSION: Laparoscopy-assisted (via Pneumosleeve) live donor nephrectomy shortens the operative time without affecting graft survival in the domestic swine model.

Animals↗
PubMed1996

Effect of octreotide on pancreatic endocrine function in partial pancreatectomy.

Octreotide acetate (Sandostatin), a long-acting somatostatin analogue, has been demonstrated to inhibit pancreatic exocrine secretion. The effect of octreotide acetate on pancreatic endocrine function in patients undergoing pancreas surgery or pancreas transplantation has not been as well described, nor have the clinical implications been studied as systematically. This study was designed to investigate the effects of octreotide acetate on glucose metabolism and endocrine function in a partial pancreatectomized canine model, simulating reduced islet cell reserve. Serum levels of glucose, insulin, and glucagon were determined at intervals over 2 hr following an intravenous glucose tolerance test (0.5 g/kg intravenous bolus of 50% glucose) in: normal animals (Group A, n = 5), normal animals pretreated with an intravenous bolus of 400 micrograms of octreotide acetate (Group B, n = 5), partial pancreatectomized animals (Group C, n = 5), and partial pancreatectomized animals pretreated with an intravenous bolus of 400 micrograms of octreotide acetate (Group D, n = 5). Peak glucose concentration was significantly increased in Group D when compared to Group C (Group C = 304.2 +/- 13.5 mg/dl vs Group D = 353.2 +/- 12.9 mg/dl, P < 0.05), indicating an impairment of glucose metabolism by octreotide. In addition, octreotide significantly decreased peak insulin release in the partial pancreatectomy groups (Group C = 129 +/- 12.9 micro U/ml vs Group D = 47.5 +/- 6.8 micro U/ml, P < 0.05). There were no significant differences in the rate of glucose utilization or glucagon concentrations among the groups. These results demonstrate that octreotide does result in insulin suppression, with a resultant increase in stimulated glucose concentrations, in a canine model of reduced islet cell mass. Further studies are required to determine the mechanism of action of octreotide on endocrine function in the setting of pancreas transplant.

Animals↗
PubMed1995

Evidence for a colonic PAF receptor.

We sought to determine the effect of exogenously administered platelet-activating factor (PAF) on eicosanoid release from the left colon of the rabbit. Using an isolated buffer-perfused rabbit left colon preparation, 1.0- or 5.0-micrograms doses of PAF were infused into the inferior mesenteric artery. Effluents from the inferior mesenteric vein and colonic lumen were collected and the concentrations of the eicosanoids, prostaglandin E, 6-ketoprostaglandin F1 alpha, thromboxane B2, and leukotriene B4 (LTB4), were measured by ELISA. During PAF infusion there was a significant increase of all prostanoids, but not LTB4 into the venous effluent and colonic luminal perfusate when compared to control experiments. Additional studies were performed by pretreating the colons with the PAF antagonists WEB-2170 or alprazolam prior to PAF infusion. Both venous and luminal effluent prostanoid release was effectively blocked by WEB-2170, but not by alprazolam. Colons pretreated with WEB-2170 prior to PAF had markedly diminished tissue injury when compared to colons treated with PAF alone. Inhibition of PAF-stimulated prostanoid release by WEB-2170 suggests that a PAF-sensitive receptor is present in rabbit colonic tissue which may induce eicosanoid-mediated tissue injury.

Animals↗
PubMed1994

Effect of platelet-activating factor and its antagonists on colonic dysmotility and tissue levels of colonic neuropeptides.

We investigated whether platelet-activating factor (PAF) alters colonic tissue levels of substance P and vasoactive intestinal peptide (VIP), two neuropeptides that regulate colonic motility. Left colons were harvested from NZ White Rabbits and underwent vascular perfusion via the inferior mesenteric artery. Strain gauge transducers were sewn onto the serosal surface of the colon to evaluate colonic motility. Colons were perfused with either buffered saline alone or with 5.0 x 10(-5) M PAF. PAF administration increased tissue VIP and substance P levels and decreased the force of colonic contractions. Pretreatment with WEB-2170 or alprazolam decreased concentrations of both tissue neuropeptides, and decreased the force of colonic contractions and minute motility index. These results suggest that both VIP and substance P are stimulated by PAF and may participate in colonic dysmotility during inflammatory states.

Alprazolam↗
PubMed1994

Platelet-activating factor mediates trinitrobenzene induced colitis.

Platelet-activating factor (PAF) is an endogenous phospholipid which may be an important mediator of shock and inflammation. Recent evidence suggests that PAF plays a role in the development of ischemic colitis and inflammatory bowel disease. Its effects are mediated by second messengers, including the arachidonic acid metabolites. Using an ex vivo isolated left colon rabbit perfusion model, our aims were to determine whether exogenously administered trinitrobenzene sulfonic acid (TNB), which produces experimental colitis, stimulates both PAF and eicosanoid release in the colon, and if so, whether this effect can be blocked by a PAF antagonist. Colonic inflammation was induced by the intracolonic administration of 0.25 ml of 50% ethanol containing 30 mg of TNB. Tissue and perfusate concentrations of the eicosanoids, [prostaglandin E (PGE2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2), leukotriene B4 (LTB4)] and the autocoid PAF were measured by ELISA. During TNB infusion there was a significant increase in tissue levels of PAF compared to control colons. Additional studies performed pretreating the colons with the PAF receptor antagonist WEB-2170 prior to TNB infusion blocked PAF release. TNB stimulated release of luminal eicosanoids except LTB4 and suppressed release of tissue prostanoids. Pretreatment with WEB-2170 prior to TNB inhibited luminal eicosanoids, and inhibited PGE2 and prostacyclin, but not TX tissue suppression. Inhibition of TNB-stimulated PAF release by WEB-2170 suggests that PAF may play a role in TNB-induced colitis and this phenomenon may mediate tissue injury.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

The effect of dimethyl PGE2 on canine pancreatic autograft exocrine secretion.

This study was designed to evaluate the effect of 16,16-dimethyl prostaglandin E2 (dimethyl PGE2) on exocrine secretion in autografted animals with pancreaticocystostomies. The rates of secretion of urinary (autograft) amylase (units/min) and bicarbonate (mmole/min), over a 5-hr interval, were determined in the basal state (Group A, N = 5), after a bolus injection of 1 microgram/kg of dimethyl PGE2 (Group B, N = 5), during an OP-CCK infusion at 125 ng/kg/hr (Group C, N = 5), and during an OP-CCK infusion plus a bolus injection of 1 microgram/kg (Group D, N = 5) or 18 micrograms/kg (Group E, N = 5) of dimethyl PGE2 at the end of the second hour. Basal secretion of amylase and bicarbonate were decreased 1 hr after 1 microgram/kg of dimethyl PGE2, with the bicarbonate inhibition being statistically significant (Group A = 0.073 +/- 0.04 vs Group B = 0.001 +/- 0.00; P less than 0.05). When compared to Group C (128.3 +/- 28.0), an immediate and significant inhibition of OP-CCK-stimulated amylase release was demonstrated in both Group D (36.3 +/- 11.1; P less than 0.02) and Group E (57.3 +/- 13.4; P less than 0.05). One and two hours post-dimethyl PGE2, amylase releases were 37.7 +/- 8.6 and 64.7 +/- 6.8 in Group D and 0.92 +/- 0.3 and 8.28 +/- 2.6 in Group E, compared to 140.3 +/- 23.3 and 104.9 +/- 31.8 in Group C, indicating a dose-related, prolonged inhibition of autograft amylase secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

16,16-Dimethylprostaglandin E2↗
PubMed1988

Cyclosporine's effect on canine pancreatic endocrine function.

This study was designed to investigate the mechanism, and reversibility, of glucose intolerance following the acute administration of cyclosporine (CsA) in a canine model. Three groups underwent a baseline intravenous glucose tolerance test (IVGTT; 0.5 g/kg of glucose), with simultaneous insulin determinations. In groups A and B, repeat IVGTTs were performed, at three-day intervals, after 2, 4, and 6 mg/kg of intravenous CsA + solvent (group A; n = 8), or the solvent alone (group B; n = 5). Repeat IVGTTs were performed in group A, 24 and 72 hr after the last CsA infusion. In group C (n = 5), IVGTTs were performed, 4, 24, 48, and 72 hr after oral CsA (12.5 mg/kg). In each group, the rate of glucose clearance (k value,--per cent min), and basal-to-peak insulin difference (uU/ml), for each IVGTT were compared with the baseline results. In group A, the basal-to-peak insulin difference was significantly lower than baseline (81.9 +/- 13.6) after 2 mg/kg (27.3 +/- 3.1; P less than 0.005), 4 mg/kg (22.7 +/- 3.7; P less than 0.001); and 6 mg/kg (16.8 +/- 3.2; P less than 0.001) of CsA, and returned to baseline within 24 hr (81.4 +/- 3.7). Corresponding K values were also significantly different in group A. In group B, there were no significant differences in these parameters from controls, at the equivalent doses of the solvent alone. At 4 hr after oral CsA (group C), there was a reduction in the basal-to-peak insulin difference (37.2 +/- 9.1 vs. 22.5 +/- 4.1) and K values (-3.20 +/- 0.4 vs. -1.96 +/- 0.3), with the change in K values being statistically significant (P less than 0.05). A return to baseline levels was present at 24 h. This study demonstrates that, in the canine model, therapeutic doses of intravenous and oral CsA acutely impair glucose regulation. This acute effect is secondary to decreased peripheral insulin levels, is reversible at 24 h, and is not evident with CsA solvent alone. The mechanism of decreased insulin secretion following CsA administration requires further elucidation.

Administration, Oral↗
PubMed1988

The effect of terbutaline on exocrine function in the denervated canine pancreas.

This study was designed to evaluate the effects of the beta adrenergic agonist, terbutaline, on pancreatic exocrine secretion in the denervated canine pancreas. In vitro assessment was performed by evaluating the effect of terbutaline on 10(-8) OP-CCK stimulated amylase release of pancreatic tissue slices incubated at 37 degrees C in Krebs-bicarbonate media. In vivo assessment was accomplished in animals with pancreatic autografts and functioning pancreaticocystostomies, by evaluating the effect of intravenous terbutaline (0.075 mg/kg over 15 min) on the basal, and OP-CCK (125 ng/kg/hr)--stimulated, rate of secretion of urinary (autograft) amylase and bicarbonate. Incubation of tissue slices with terbutaline had no significant effect on OP-CCK-stimulated amylase release. The intravenous terbutaline infusion resulted in a decrease in the basal rate of amylase (U/min) and bicarbonate (mmol/min) secretion, with the bicarbonate inhibition being significantly decreased, when compared with controls (0.073 +/- .04 vs. 000 +/- .00; P less than 0.05). Following the terbutaline infusion, there was also a significant decrease in OP-CCK-stimulated amylase (140.3 +/- 23.3 vs. 24.6 +/- 11.9; P less than 0.005) and bicarbonate release (.069 +/- .03 vs. .003 +/- .001; P less than 0.05). This inhibition persisted until the study was terminated 3 hr after the terbutaline infusion. These studies demonstrate that terbutaline causes a significant and prolonged decrease in autograft exocrine secretion--and, as a result, may have a therapeutic role in reducing the exocrine complications associated with pancreatic transplantation. The mechanism of action of this agent in the denervated pancreas requires further elucidation.

Amylases↗
PubMed1985

Oxidation-reduction maintenance in organ preservation.

The isolated perfused organ is more sensitive to the toxicity of oxygen since hypothermia reduces the activities of enzymes responsible for minimizing oxygen toxicity. To protect the organ under these conditions reducing agents must be added to the perfusate. Quantitation of the resulting reduction is best obtained by measurement of the oxidation-reduction potential of the perfusate. A device was designed for this purpose and, by electrochemical principle, controlled reduction of the oxidized form of the oxidation-reduction couple was affected. Kidneys were perfused with cryoprecipitated plasma. With the electrochemical cell in the circuit, the oxidation-reduction potential of the perfusate was adjusted by the addition of ascorbic acid and glutathione and the cell was driven by a battery-powered potentiostat. Kidneys subjected to 60 minutes of warm ischemia had optimal survival at -20 mV. Preservation for six days in a monitored group had no survivors, whereas kidneys with oxidation-reduction support maintained life. Optimal oxidation-reduction support maintained life. Optimal oxidation-reduction was at or near -17 mV. These data show a requirement of an optimal oxidation-reduction potential to reverse warm ischemia damage and to prolong the period of ex vivo preservation of isolated perfused organ.

Animals↗
PubMed1985

An experimental evaluation of nucleotide enhancement techniques for kidney transplantation.

The effect of various nucleotide-enhancing agents on renal function and intracellular nucleotide levels was evaluated in a canine autotransplant model. Thirty-five dogs (18-28 kg) underwent left nephrectomy and 30 min of warm ischemia followed by Collins C-4 flush and 24 hr of cold-storage preservation. Heterotopic autotransplantation and immediate contralateral nephrectomy was then performed. Seven equal groups were evaluated: group A--controls, group B--adenosine pretreatment (1.0 g), group C--dipyridamole pretreatment (10 mg), group D--adenosine (1.0 g), and dipyridamole (10 mg) pretreatment, group E--adenosine (200 mg) and EHNA (2.5 mg/kg) pretreatment, group F--adenosine (200 mg) and EHNA (2.5 mg/kg) in the Collins C-4 flush, and group G--adenosine (200 mg) and EHNA (2.5 mg/kg) at the time of autotransplantation. All kidneys underwent cortical biopsies at the end of preservation and 1 hr after restoration of blood flow for determinations of AMP, ADP, and ATP. In the pretreatment groups (groups B through E) there was 60% graft survival whereas the controls (group A) and the groups treated after ischemia (groups F and G) had 0, 0, and 20% graft survival, respectively. In groups B and E, ATP levels were greater than controls after preservation and 1 hr after restoration of blood flow. Group C AMP and ADP levels and group D energy charge were greater than controls in the post-transplantation biopsies. Administration of adenosine and EHNA after ischemia was not associated with increased intracellular nucleotide levels. One hour post-transplantation biopsies demonstrated greater ability to regenerate cortical nucleotides in the surviving animals but no absolute value could be identified as a predictor of viability. In conclusion, pretreatment with adenosine, dipyridamole, and EHNA alone and in combination is beneficial in ischemically injured kidneys undergoing cold-storage preservation.

Adenine↗
PubMed1984

A comparison of ductal management techniques in an in situ canine pancreas model.

Twenty-five dogs underwent right pancreatectomy leaving the tall of the pancreas in situ. Five equal groups underwent either intraperitoneal drainage (open-duct group), duct ligation, acrylate glue occlusion, neoprene glue occlusion, or Roux-en-Y pancreaticojejunostomy. On day 21 the tall of the pancreas was removed and on day 28 the dogs were killed. Daily serum glucose and amylase and biweekly insulin determinations were performed, and intravenous glucose tolerance tests ( IVGTTs ), with simultaneous insulin assays, were carried out before and after distal pancreatectomy. The mean daily blood glucose level prior to distal pancreatectomy was 95.6 +/- 3.2 mg/dL in the open-duct group, 91.6 +/- 3.0 mg/dL in the ligation group, 94.0 +/- 4.0 mg/dL in the acrylate group, 226.3 +/- 56.6 mg/dL in the neoprene group, and 94.1 +/- 2.6 mg/dL in the Roux-en-Y group. Mean K values (rate constant of glucose clearance) were as follows: open-duct group, -0.907+ +/- 0.240% per minute; ligation group, -1.024% +/- 0.253% per minute; acrylate group, -0.820% +/- 0.087% per minute; neoprene group, -0.526% +/- 0.186% per minute; and Roux-en-Y group, -1.399% +/- 0.566% per minute (normal, -2.201% +/- 0.388% per minute). Insulin release during IVGTT (basal to peak insulin difference) was greatest in the open-duct and Roux-en-Y groups. Although glucose clearance and insulin release were optimal with pancreaticojejunostomy, peripancreatic complications developed in two of the five dogs. In conclusion, the open-duct technique and Roux-en-Y pancreaticojejunostomy result in optimal endocrine function in this in situ model. Due to its simplicity, the open-duct technique is most suitable for further laboratory investigations of segmental pancreatic transplantation.

Acrylic Resins↗
PubMed1983

The effects of ATP-MgCl2 and dipyridamole in cold-storage preservation.

The effects of ATP-MgCl2 and dipyridamole were evaluated in a canine model. Twenty-five adult mongrel dogs were divided into five equal groups. All dogs underwent left nephrectomy and 30 min of warm ischemia followed by Collins' C-4 flush and 24 hr of cold-storage preservation. Heterotopic autotransplantation and immediate contralateral nephrectomy were then performed. Group A served as controls; Group B was pretreated with intravenous ATP-MgCl2 (2.5 mM); Group C with intravenous dipyridamole (10 mg), and Group D with both ATP-MgCl2 (2.5 mM) and dipyridamole (10 mg). Group E was treated with ATP-MgCl2 (2.5 mM) at the time of transplantation. All kidneys underwent cortical biopsies at the end of preservation and 1 hr after restoration of blood flow for determinations of AMP, ADP, and ATP. In Groups A and E there were no survivors, whereas Groups B, C, and D had 40, 60, and 40% graft survival. In Groups B and D, ATP and energy charge (EC) were greater than that of controls after 24 hr of preservation, with Group D values being significantly greater (P less than 0.01). AMP and ADP levels were significantly greater (P less than 0.02) in Group C when compared to Group A. One hour posttransplantation biopsies demonstrated greater ability to regenerate cortical nucleotides in the surviving animals, but no absolute value could be identified as a predictor of viability. In conclusion, pretreatment with ATP-MgCl2 or dipyridamole maintains intracellular nucleotide levels and has a beneficial effect on graft survival in ischemically injured kidneys undergoing cold-storage preservation.

Adenine Nucleotides↗
PubMedDate not supplied

A laboratory model for evaluation of posttransplant pancreatic exocrine secretion.

Monitoring of urinary enzymuria has been utilized to detect allograft dysfunction after pancreas transplantation with pancreaticocystostomy. In addition, pharmacologic exocrine suppression has been advocated to minimize bicarbonate and protein wasting. Ensuring the validity of these approaches requires controlling both for immunologic alterations in transplant function and for the renal excretion of amylase, bicarbonate, and protein. Toward this end, adult mongrel dogs were divided into two groups. Group A animals underwent distal pancreatectomy alone, and group B animals underwent distal pancreatectomy with autotransplantation and pancreaticocystostomy. In each group, amylase, bicarbonate, and protein output were determined over a 5-hour period in the basal state, during a continuous infusion of octapeptide-cholecystokinin (OP-CCK) at 125 ng/kg/hour, and during a continuous infusion of OP-CCK (125 ng/kg/hour) plus a bolus injection of one clinical unit of secretion per kilogram. Bicarbonate output was not significantly different in the groups with and without autografts. Compared to nonautograft experiments, a statistically significant increase in amylase output was demonstrated in the autograft animals. An increase in protein output was also demonstrated in the autograft experiments, and this increase was statistically significant in the OP-CCK group and the OP-CCK and secretin group. In addition, compared to basal autograft secretion, OP-CCK and OP-CCK plus secretin stimulation resulted in a sustained and significant increase in urinary amylase and protein secretion, indicating preserved sensitivity of the denervated pancreas to exogenous hormones. These results indicate that the canine segmental pancreatic autograft model with pancreaticocystostomy is a suitable model to identify agents associated with exocrine inhibition after transplantation.

Amylases↗