scholarly journals Second-Generation Recombinant Hemoglobin Molecules Do Not Stimulate Sphincter of Oddi, Gallbladder, or Duodenal Motility in the Australian Brush-Tailed Possum

2004 ◽  
Vol 18 (7) ◽  
pp. 441-448 ◽  
Author(s):  
Shunichi Takahata ◽  
Hiroyuki Konomi ◽  
Ann C Schloithe ◽  
James Toouli ◽  
Gino TP Saccone
Keyword(s):  
Blood Pressure ◽  
Second Generation ◽  
Binding Capacity ◽  
Sphincter Of Oddi ◽  
Blood Substitutes ◽  
Gallbladder Motility ◽  
High Dose ◽  
Oxygen Carriers ◽  
Duodenal Motility ◽  
Biliary Motility

BACKGROUND:Several studies have investigated the effects of hemoglobin-based oxygen carriers on gastrointestinal motility. Diaspirin cross-linked hemoglobin reduces sphincter of Oddi trans-sphincteric flow and increases duodenal motility in the Australian brush-tailed possum, effects attributed to nitric oxide (NO) scavenging. Recently, second-generation recombinant hemoglobin molecules with reduced NO scavenging ability have been developed.AIM:To determine the effects of two second-generation recombinant hemoglobin solutions and the prototype recombinant hemoglobin with high NO binding, on duodenal and biliary motility in the Australian brush-tailed possum.METHOD:Blood pressure; duodenal, sphincter of Oddi and gallbladder motility; and trans-sphincteric flow were recorded. The effects of recombinant hemoglobin or human serum albumin (control) solutions on these parameters were investigated. Each solution was infused intravenously at 1 mL/kg/min to deliver 250 mg/kg or 500 mg/kg.RESULTS:Duodenal contraction frequency was stimulated by the high dose of prototype recombinant hemoglobin, but not by a comparable dose of second-generation recombinant hemoglobin. The induced duodenal activity occurred in the later phase of the experimental period. In contrast, biliary motility and trans-sphincteric flow were not altered by any hemoglobin solution. The high dose of all the hemoglobin solutions elevated blood pressure, whereas the low dose solutions did not alter any parameter measured.CONCLUSION:At the doses studied, the second-generation recombinant hemoglobin with reduced NO binding capacity did not significantly alter duodenal and biliary motility, supporting the need for further studies to evaluate their potential usefulness as blood substitutes.

Do motilin and pancreatic polypeptide regulate duodenal bile acid delivery?

1988 ◽  
Vol 66 (12) ◽  
pp. 1499-1504
Author(s):  
R. B. Scott ◽  
S. C. Diamant ◽  
G. R. Greenberg
Keyword(s):  
Bile Acid ◽  
Pancreatic Polypeptide ◽  
Plasma Levels ◽  
Sphincter Of Oddi ◽  
Gallbladder Motility ◽  
Gallbladder Contraction ◽  
Postprandial Period ◽  
Standard Meal ◽  
Duodenal Motility ◽  
Plasma Motilin

The plasma levels of the enteric hormones, motilin and pancreatic polypeptide, cycle in association with fasting intestinal motility and are altered by feeding. Intravenous administration of motilin causes gallbladder contraction and increased sphincter of Oddi phasic motor activity, whereas pancreatic polypeptide causes gallbladder relaxation. To determine if endogenous plasma levels of motilin and pancreatic polypeptide control sphincter of Oddi and gallbladder motility, and regulate duodenal bile acid delivery, we measured during fasting and after feeding the correlation between (a) changes in plasma motilin or pancreatic polypeptide, and (b) the duodenal delivery of a steady-state hepatic output of radiolabelled bile acid. Four dogs were prepared with duodenal cannulas. Duodenal motility was recorded manometrically. Plasma levels of pancreatic polypeptide and motilin were determined during a full cycle of the migrating myoelectric complex for 20 min before and 40 min after ingestion of a standard meal. To assess the effect of the sphincter of Oddi and the gallbladder together, or the gallbladder alone on duodenal bile acid delivery, the dogs received a continuous i.v. infusion of [14C]taurocholic acid (TCA); duodenal delivery of TCA was quantitated with the sphincter of Oddi intact using duodenal marker perfusion, or with the sphincter of Oddi cannulated and zero outflow resistance. In the interdigestive period with the sphincter of Oddi intact, only 0.1 (r2) of the variance of duodenal bile acid delivery can be predicted from the variance of motilin, and the correlation of plasma pancreatic polypeptide with duodenal TCA delivery is opposite that expected if pancreatic polypeptide caused gallbladder relaxation. In the interdigestive period with the sphincter of Oddi cannulated, or in the postprandial period with the sphincter of Oddi intact or cannulated, the correlations of plasma motilin and pancreatic polypeptide with duodenal TCA delivery are opposite those expected if motilin induces gallbladder contraction, and pancreatic polypeptide induces gallbladder relaxation. Assuming these mechanisms, a causal association between variation in plasma motilin or pancreatic polypeptide and interdigestive or postprandial duodenal bile acid delivery is unlikely.

The biochemistry of drugs and doping methods used to enhance aerobic sport performance

2008 ◽  
Vol 44 ◽  
pp. 63-84 ◽  
Author(s):  
Chris E. Cooper
Keyword(s):  
Oxygen Uptake ◽  
Oxygen Content ◽  
Oxygen Delivery ◽  
Sport Performance ◽  
Blood Substitutes ◽  
Altitude Training ◽  
Blood Oxygen ◽  
Oxygen Carriers ◽  
Sports Performance ◽  
Blood Doping

Optimum performance in aerobic sports performance requires an efficient delivery to, and consumption of, oxygen by the exercising muscle. It is probable that maximal oxygen uptake in the athlete is multifactorial, being shared between cardiac output, blood oxygen content, muscle blood flow, oxygen diffusion from the blood to the cell and mitochondrial content. Of these, raising the blood oxygen content by raising the haematocrit is the simplest acute method to increase oxygen delivery and improve sport performance. Legal means of raising haematocrit include altitude training and hypoxic tents. Illegal means include blood doping and the administration of EPO (erythropoietin). The ability to make EPO by genetic means has resulted in an increase in its availability and use, although it is probable that recent testing methods may have had some impact. Less widely used illegal methods include the use of artificial blood oxygen carriers (the so-called ‘blood substitutes’). In principle these molecules could enhance aerobic sports performance; however, they would be readily detectable in urine and blood tests. An alternative to increasing the blood oxygen content is to increase the amount of oxygen that haemoglobin can deliver. It is possible to do this by using compounds that right-shift the haemoglobin dissociation curve (e.g. RSR13). There is a compromise between improving oxygen delivery at the muscle and losing oxygen uptake at the lung and it is unclear whether these reagents would enhance the performance of elite athletes. However, given the proven success of blood doping and EPO, attempts to manipulate these pathways are likely to lead to an ongoing battle between the athlete and the drug testers.

Pre-emptive Analgesia for Postoperative Pain Relief in Children – Role of Paracetamol

2009 ◽  
pp. 9-16
Author(s):  
Rubina Yasmin ◽  
AKM Akhtaruzzaman ◽  
Paresh Chandra Sarker ◽  
Neaz Ahmed ◽  
Ranadhir Kumar Kundu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Postoperative Pain ◽  
Diclofenac Sodium ◽  
Total Duration ◽  
Pain Scale ◽  
Prospective Clinical Study ◽  
High Dose ◽  
Induction Of Anaesthesia

This prospective clinical study was carried out in the Dept. of Anaesthesia, Analgesia and Intensive Care Medicine, BSMMU, Dhaka, during the period of May 2003 to July 2003. The study was done to emphasize the importance of giving analgesics preemptively instead of waiting for the child to complain of pain and to produce smooth recovery after surgery by decreasing immediate postoperative pain in children by a simple, safe acceptable drug. The children scheduled for tonsillectomy under general anaesthesia were recruited in this study. The analgesic efficiency of rectal paracetamol in two doses, 25 mg/kg bodywt.(Gr-P25) and 50 mg/kg. bodywt. (Gr-P50) were compared with Diclofenac Sodium suppository 1mg/ kg body weight (Gr-D) given half an hour before induction of anaesthesia. Pain scoring was done by TPPPS (Toddler Pre-schooler postoperative pain scale). Heart rate and blood pressure were stable in Gr-P50 and Gr-D. Time of first demand of analgesic was delayed in Gr-P50 and Gr-D. Total paracetamol consumption in 24 hours was less in Gr-P50(181±14.25) and Gr-D (212±25) than Gr-P25(318± 26.39). Total duration of analgesia in Gr- P50 (657±9.94) mins. and in Gr- D(502±10.63) mins. and in Gr-P25(288±23.17) mins. Pre-emptive high dose rectal paracetamol appears to be more effective than diclofenac sodium suppository for postoperative analgesia in children undergoing tonsillectomy. Journal of BSA, Vol. 18, No. 1 & 2, 2005 p.9-16

High-dose Cholecalciferol Supplementation Reducing Morning Blood Pressure in Normotensive DM1 Patients

2020 ◽  
Vol 16 ◽  
Author(s):  
Natércia Neves Marques de Queiroz ◽  
Franciane Trindade Cunha de Melo ◽  
Fabrício de Souza Resende ◽  
Luísa Corrêa Janaú ◽  
Norberto Jorge Kzan de Souza Neto ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vitamin D ◽  
Blood Pressure Monitoring ◽  
Vitamin D Supplementation ◽  
High Dose ◽  
Before And After ◽  
Patients With Diabetes ◽  
Morning Blood Pressure ◽  
Cholecalciferol Supplementation ◽  
Lipids Profile

Background: Vitamin D (VD) deficiency has been related to several endocrine metabolic and cardiovascular diseases. Effect of VD supplementation on blood pressure (BP) in patients with diabetes is controversial. Objective: The aim of this study was to evaluate high-dose vitamin D supplementation effects on blood pressure of normotensive type 1 diabetes mellitus (T1DM) patients by 24-hour ambulatory blood pressure monitoring (ABPM). Methods: We performed a clinical trial including 35 T1DM normotensive patients, who received doses of 4,000 or 10,000 IU/day of cholecalciferol for 12 weeks according to previous VD levels. They underwent 24-hour ABPM, along with glycated hemoglobin, creatine, lipids profile and PCRus dosage before and after VD supplementation. Results and discussion: We found an expressive reduction of systolic and diastolic morning blood pressures (117±14 vs 112±14, p<0,05; 74±9 vs 70±10 mmHg, p<0,05, respectively) with no changes in other pressoric markers. Besides, we noticed a relation between levels of VD after supplementation and diastolic morning blood pressure (r= -0,4; p<0.05). Conclusion: Our study suggests an association between supplementation of high doses of vitamin D and the reduction of morning blood pressure in normotensive T1DM patients.

Methylprednisolone on circulating eicosanoids and vasomotor tone after endotoxin

1986 ◽  
Vol 61 (1) ◽  
pp. 185-191 ◽  
Author(s):  
C. A. Hales ◽  
R. D. Brandstetter ◽  
C. F. Neely ◽  
M. B. Peterson ◽  
D. Kong ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Resistance ◽  
Systemic Blood Pressure ◽  
Physiological Effect ◽  
High Dose ◽  
Systemic Blood ◽  
Eicosanoid Production ◽  
Circulating Levels

Acute pulmonary and systemic vasomotor changes induced by endotoxin in dogs have been related, at least in part, to the production of eicosanoids such as the vasoconstrictor thromboxane and the vasodilator prostacyclin. Steroids in high doses, in vitro, inhibit activation of phospholipase A2 and prevent fatty acid release from cell membranes to enter the arachidonic acid cascade. We, therefore, administered methylprednisolone (40 mg/kg) to dogs to see if eicosanoid production and the ensuing vasomotor changes could be prevented after administration of 150 micrograms/kg of endotoxin. The stable metabolites of thromboxane B2 (TxB2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) were measured by radioimmunoassay. Methylprednisolone by itself did not alter circulating eicosanoids but when given 2.5 h before endotoxin not only failed to inhibit endotoxin-induced eicosanoid production but actually resulted in higher circulating levels of 6-keto-PGF1 alpha (P less than 0.05) compared with animals receiving endotoxin alone. Indomethacin prevented the steroid-enhanced concentrations of 6-keto-PGF1 alpha after endotoxin and prevented the greater fall (P less than 0.05) in systemic blood pressure and systemic vascular resistance with steroid plus endotoxin than occurred with endotoxin alone. Administration of methylprednisolone immediately before endotoxin resulted in enhanced levels (P less than 0.05) of both TxB2 and 6-keto-PGF1 alpha but with a fall in systemic blood pressure and vascular resistance similar to the animals pretreated by 2.5 h. In contrast to the early steroid group in which all of the hypotensive effect was due to eicosanoids, in the latter group steroids had an additional nonspecific effect. Thus, in vivo, high-dose steroids did not prevent endotoxin-induced increases in eicosanoids but actually increased circulating levels of TxB2 and 6-keto-PGF1 alpha with a physiological effect favoring vasodilation.

Influence of motilin and cholecystokinin on sphincter of Oddi and duodenal mobility

1987 ◽  
Vol 253 (5) ◽  
pp. G679-G683 ◽  
Author(s):  
E. L. Muller ◽  
P. A. Grace ◽  
R. L. Conter ◽  
J. J. Roslyn ◽  
H. A. Pitt
Keyword(s):  
Sphincter Of Oddi ◽  
Prairie Dogs ◽  
Prairie Dog ◽  
Cholecystokinin Octapeptide ◽  
Side Hole ◽  
Hole Pressure ◽  
Duodenal Motility ◽  
Sphincter Of Oddi Motility ◽  
Duodenal Lumen ◽  
Distal Port

The sphincter of Oddi and the duodenum exhibit cyclical activity in phase with the migrating myoelectric complex. Both motilin and cholecystokinin have been shown to modulate gastrointestinal and sphincter of Oddi motility. However, previous studies have not monitored the effects of these hormones on simultaneously recorded sphincter of Oddi and duodenum pressures. The present investigation was undertaken, therefore, to determine the influence of both motilin and cholecystokinin on simultaneously recorded sphincter of Oddi and duodenal motility. In seven anesthetized prairie dogs, a triple-lumen, side-hole, pressure-monitored perfusion catheter was positioned with the proximal port in the sphincter of Oddi and the distal port in the duodenal lumen. Sphincter of Oddi and duodenal motility was recorded before and during 20-min infusions of motilin and cholecystokinin octapeptide (CCK-8) at 1, 10, and 100 ng.kg-1.min-1. Both hormones produced dose-related increases in sphincter of Oddi and duodenal motility. No response was observed with either hormone at 1 ng.kg-1.min-1. At 10 ng.kg-1.min-1, the duodenum was slightly more sensitive to motilin than to CCK-8, while the sphincter of Oddi was equally affected by both hormones. At 100 ng.kg-1.min-1, both hormones stimulated the sphincter of Oddi and the duodenum equally. These data indicate that in the prairie dog, both motilin and cholecystokinin stimulate sphincter of Oddi and duodenal motility.

Solumedrol Treatment for Severe Sepsis in Humans with a Blunted Adrenocorticotropic Hormone-Cortisol Response: A Prospective Randomized Double-Blind Placebo-Controlled Pilot Clinical Trial

2021 ◽  
pp. 088506662110388
Author(s):  
Divya Birudaraju ◽  
Sajad Hamal ◽  
John A. Tayek
Keyword(s):  
Blood Pressure ◽  
Clinical Trial ◽  
Adrenocorticotropic Hormone ◽  
Serum Cortisol ◽  
High Dose ◽  
Cortisol Response ◽  
Acth Stimulation ◽  
Double Blind ◽  
Significant Difference ◽  
To Receive

Purpose To test the benefits of Solumedrol treatment in sepsis patients with a blunted adrenocorticotropic hormone (ACTH)-cortisol response (delta <13 µg/dL) with regard to the number of days on ventilator, days on intravenous blood pressure support, length of time in an intensive care unit (ICU), 14-day mortality, and 28-day mortality. The trial was prospective, randomized, and double-blind. As part of a larger sepsis trial, 54 patients with sepsis had an intravenous ACTH stimulation test using 250 µg of ACTH, and serum cortisol was measured at times 0, 30, and 60 min. Eleven patients failed to increase their cortisol concentration above 19.9 µg/dL and were excluded from the clinical trial as they were considered to have adrenal insufficiency. The remaining 43 patients had a baseline cortisol of 32 ± 1 µg/dL increased to 38 ± 3 µg/dL at 30 min and 40 ± 3 at 60 min. All cortisol responses were <12.9 µg/dL between time 0 and time 60, which is defined as a blunted cortisol response to intravenous ACTH administration. Twenty-one were randomized to receive 20 mg of intravenous Solumedrol and 22 were randomized to receive a matching placebo every 8 h for 7-days. There was no significant difference between the two randomized groups. Data analysis was carried out bya two-tailed test and P < .05 as significant. Results Results: The mean age was 51 ± 2 (mean ± SEM) with 61% female. Groups were well matched with regard to APACHE III score in Solumedrol versus placebo (59 ± 6 vs 59 ± 6), white blood cell count (18.8 ± 2.2 vs 18.6 ± 2.6), and incidence of bacteremia (29 vs 39%). The 28-day mortality rate was reduced in the Solumedrol treated arm (43 ± 11 vs 73 ± 10%; P < .05). There was no change in days in ICU, days on blood pressure agents, or days on ventilator. Seven days of high-dose intravenous Solumedrol treatment (20 mg every 8 h) in patients with a blunted cortisol response to ACTH was associated with an improved 28-day survival. This small study suggests that an inability to increase endogenous cortisol production in patients with sepsis who are then provided steroid treatment could improve survival.

scholarly journals An observational study on patient compliance and adverse drug reactions of antihypertensives drugs in a tertiary care center of Bihar

2021 ◽  
Vol 6 (4) ◽  
pp. 190-193
Author(s):  
Mrityunjay Kumar Pandit ◽  
Kumar Gaurav ◽  
Jeetendra Kumar
Keyword(s):  
Blood Pressure ◽  
Combination Therapy ◽  
Antihypertensive Drugs ◽  
Care Center ◽  
Adult Population ◽  
Tertiary Care ◽  
Cross Sectional Study ◽  
High Dose ◽  
Cross Sectional ◽  
Institutional Ethics

Hypertension is among the most common non-communicable and lifestyle disease in our country that affects adult population of both the genders from all socio-economic backgrounds and urban and rural population. In-spite of this, early diagnosis and appropriate treatment are suboptimal. Adherence of prescribed treatment has been studied in patients of hypertension in this study. : An observational and cross-sectional study was conducted in the Department of Pharmacology, Jawahar Lal Nehru Medical College and Hospital, Bhagalpur, Bihar. Prior to the initiation of the study, clearance was obtained from the Institutional Ethics Committee. Study period was between January 2021 and June 2021.A predesigned pretested interview schedule was used to collect the data from the 247 study participants. This schedule contained information related to socio-demographic variables, comorbidity, a format to assess the compliance to antihypertensive drugs prescribed and any adverse event. : A significant improvement in maintain optimal in blood pressure was observed in patients treated with one pill per day as compared to patients prescribed with two and three pills per day. Compliance was significantly better in patients in combination therapy as compared to monotherapy. : Low dose combination therapy has been stated to be more effective than high dose monotherapy in controlling blood pressure. It shows better compliance and lesser incidence of side-effects.

scholarly journals An observational comparative study of different doses of azilsartan and with chlorthalidone combination in moderate hypertension

2019 ◽  
Vol 8 (2) ◽  
pp. 259
Author(s):  
Tamoghna Maiti ◽  
Sonai Mandal ◽  
Ratul Banerjee ◽  
Sourav Chakrabarty ◽  
Amrita Panda
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Antihypertensive Agents ◽  
Fixed Dose ◽  
High Dose ◽  
Hypertensive Patients ◽  
Medical College ◽  
Fda Approval ◽  
High Prevalence ◽  
Dose Combination

Background: High blood pressure (BP) is one of the significant non-communicable diseases that are of high prevalence in our country. Hypertension (HTN) is responsible cause of 57% of stroke and 24% of coronary heart disease deaths in India. Eight classes of medications are currently used in the treatment of hypertension. Azilsartan medoxomil is a newly added FDA approved drug to the ARB class of antihypertensive agents. azilsartan and chlorthalidone combination is also got the FDA approval. There is limited study in between these two groups regarding efficacy especially in rural Bengal.Methods: A prospective observational study was done in medicine OPD of Bankura Sammilani Medical College for twelve weeks with two groups that are azilsartan (80mg) and fixed dose combination of azilsartan (40mg) plus chlorthalidone (12.5mg) in the age group of 18 to 55years of moderate hypertensive patients. Change of heart rate was assessed as safety parameter.Results: It was found that both the group of drugs are very much effective in lowering blood pressure constantly in respect of both systolic and diastolic BP but azilsartan monotherapy in high dose reduce systolic blood pressure slightly high. Significant change of heart rate was not seen with both the groups.Conclusions: Both the group was effective as well as safe in hypertensive patients.

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