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Biomedical subjects

P Rooth

Publications and source records attributed to P Rooth.

At least 19 recordsLinked to original sources

Short-term effects of sibutramine (Reductil) on appetite and eating behaviour and the long-term therapeutic outcome.

OBJECTIVE: To evaluate the short-term effects of sibutramine on appetite and eating behaviour and whether these effects are related to the long-term therapeutic outcome. STUDY DESIGN: Short-term: randomised, double-blind, placebo-controlled, within-subject design. Long-term: prospective open clinical trial. SUBJECTS: A total of 36 obese (nine men/27 women) with a body mass index of 39.3+/-4.3 (mean+/-s.d.) (range 30.2 - 45.2) kg/m(2) and age 44.4+/-12.1 y. PROCEDURE AND METHODS:: First phase-short-term effects: At baseline, the subjects were treated for 14 days with 15 mg sibutramine/placebo (period 1) followed by a 2 weeks single-blind placebo washout period, the subjects received the alternative therapy for another 14 days (period 2). At baseline, and at day 14 in each treatment period the subjects arrived fasting to the laboratory for a standardised breakfast and an ad libitum standardised lunch using the VIKTOR set-up (a universal eating monitor) to evaluate the microstructure of the eating behaviour (ie amount of food consumed and eating rate). Visual Analogue Scales were applied before and after the meals as well as every hour between the meals to monitor the appetite. During this first phase, subjects were encouraged to keep their habitual eating habits. Second phase-long-term effects: All subjects received 10 months open treatment with 15 mg sibutramine and dietary advice in monthly group sessions with a dietitian. On the last day of this treatment period, the subjects returned to repeat the measurements of appetite and eating behaviour using the same test procedure as during the first phase of the study. RESULTS: First phase: Sibutramine influenced appetite and eating behaviour that could be registered after only 14 days of treatment. The amount of food consumed at lunch on VIKTOR was reduced by 16% by sibutramine compared to placebo, 335+/-123 g vs 399+/-126 g (P<0.0001). Second phase: Responders and nonresponders were defined as those who ate less vs more food on VIKTOR when treated with sibutramine compared to the baseline food intake in the first phase of the study. The weight reduction was greater for responders 11.8+/-6.2 (mean+/-s.d.) kg compared to nonresponders 6.8+/-2.7 (mean+/-s.d.) kg (P<0.05). CONCLUSION: Short-term effects of sibutramine on appetite and eating behaviour were identified such as a reduction in food intake and in ratings of subjective motivation to eat. Short-term sibutramine effects on eating behaviour are to some extent related to the long-term therapeutic outcome in obese subjects.

Adult↗

Success rate of Orlistat in primary-care practice is limited by failure to follow prescribing recommendations: the referral letter content vs clinical reality.

Numerous referrals to our Obesity Unit state that 'treatment with Orlistat did not work'. This surprised us, since Orlistat has been well documented to result in long-term sustained moderate weight loss. A simple questionnaire to 70 such patients, however, revealed that in many cases the referral physician had not observed basic rules and regulations, nor given appropriate information on Orlistat use.

Adult↗

Intake of sweet foods and counts of cariogenic microorganisms in relation to body mass index and psychometric variables in women.

OBJECTIVE: As a part of the SPAWN (Stockholm Pregnancy and Women's Nutrition) study, the intake of sweet foods (habitual and pre-menstrual intakes) and the number of cariogenic microorganisms in saliva was analysed in relation to body mass index (BMI) and psychometric variables. DESIGN: A cross-sectional study. SUBJECTS: Three hundred and sixty-two women with a median BMI of 24.2 kg/m(2) (range 17.5-47.8) and 45 y of age (range 34-64). METHODS: A questionnaire of sweet food intake, salivary counts of mutans streptococci and lactobacilli and a self-rating scale on psychometric variables (CPRS-S-A). RESULTS: The number of mutans streptococci correlated with BMI (P<0.05), indirectly indicating a higher intake of sweet foods in obese women. The reported energy intake of sweet foods (more specifically the intake of chocolate), correlated with CPRS scores (P<0.01), indicating that women with more severe psychiatric symptomatology have higher intakes of sweet foods. CONCLUSIONS: This study suggests that women with higher CPRS score have higher energy intakes of sweet foods, indicating a possible link between mood regulation and the intake of sweet food. SPONSORSHIP: Karolinska Institute Research Funds.

Adult↗

Effect of serotonin reuptake inhibitor on syndrome development in obese hyperglycemic mice (Umeå ob/ob).

These experiments tested the effect of 10 to 30 mg, citalopram/kg body weight on food intake, weight increase, and blood glucose levels in young obese hyperglycemic mice (Umeå ob/ob). A leptin defect in ob/ob mice results in hyperphagia, hyperglycemia, and increased body weight compared with normal mice. Citalopram had no effect on weight increase in ob/ob mice aged 3 to 10 weeks, when the weight increase is most rapid. Citalopram reduced the weight increase at the age 10 to 19 weeks. Food intake reaches a maximum at age 7 to 10 weeks and then decreases. The reduction was more rapid in citalopram-treated mice. The weight of feces paralleled the food intake. Citalopram treatment had no effect on serum insulin levels in 15-week-old mice. Blood sugar values in fed mice reached a peak at age 7 weeks (21.7 +/- 1.7 mmol/L in controls and 22.3 +/- 1 mmol/L in citalopram-treated mice). After that, blood sugar values decreased. The decrease was more pronounced in citalopram-treated mice (P < .01 compared with controls). Blood glucose levels were lower at ages 12 to 15 weeks in female ob/ob control mice (13.6 +/- 2.5 mmol/L v 19.0 +/- 0.6 mmol/L in male control mice; P < .05). The effect of citalopram was the same in male and female mice. There was a close correlation between accumulated food intake and blood glucose values in individual animals. At age 3 to 10 weeks, ob/ob mice have a high beta-cell proliferation rate, and they have large islets of Langerhans. This was not affected by citalopram treatment. Our findings show that the serotonergic system plays a role as a regulator of food intake over shorter periods, and this is also true in the absence of leptin.

Aging↗

Initial increase and subsequent loss of vasoactive intestinal polypeptide immunoreactivity in acetylcholinesterase-positive neurons of mouse islets transplanted to the kidney.

Collagenase-isolated pancreatic islets from C57BL/6J mice were cultured overnight and transplanted under the kidney capsule of non-diabetic syngeneic hosts. Cryostat sections of grafts and fresh islets were stained for acetylcholinesterase (AChE) and vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI). Immediately after isolation, as well as 2-5 days after transplantation, VIP-LI- and AChE-positive nerve cell bodies were clearly seen in the periphery of the islets. Grafts 3-5 days old exhibited a transient and marked increase in VIP-LI nerve cell bodies and fibres. Seven days after transplantation VIP-LI nerve structures began to decrease in number and after 26-52 weeks they were no longer detectable. In contrast, AChE-positive nerve cell bodies and fibers, which showed a relatively constant pattern of distribution, were observed throughout the entire observation period. Restaining experiments demonstrated the coexistence of VIP-LI and AChE activity in the neurons. It is concluded that the grafts were extensively equipped with an intrinsic VIP-ergic and AChE-positive innervation. The initial, transient enhancement of VIP-LI expression probably reflects an adaptation of the neuro-insular complex to the preganglionic denervation, or to the ectopic environment, or both.

Acetylcholinesterase↗

Effects of isosmolar contrast media on the renal cortical blood flow in mice.

PURPOSE: In vivo fluorescence microscopy was used in experimental studies of renal cortical microcirculation in mice. The effects of i.v. infusion of a nonionic monomeric contrast medium (iohexol), a nonionic dimeric contrast medium (iodixanol), and mannitol of corresponding osmolalities were studied. RESULTS: All infusions produced marked effects on the distribution and velocity of renal cortical blood flow. Renal cortical blood flow was inhomogeneous as regards the different capillaries. There was an initial rapid rise in the blood flow in some capillaries after all infusions, while decreased flow was seen in other capillaries. The initial increase in renal cortical blood flow (RCBF) was significantly (p < 0.05) more pronounced after infusion of iohexol than after infusion of mannitol 0.69 mol/l. In all other respects, the effects of contrast media on RCBF were the same as the effects of mannitol solutions with a corresponding osmolality. The effects of each contrast medium were the same as those of mannitol of corresponding osmolality. In the capillaries showing increased blood flow, the peak value was encountered slightly later after the infusion of iodixanol than after the infusion of iohexol. This was considered to be related to differences in viscosity rather than osmolality. CONCLUSION: The difference in osmolality between iodixanol and iohexol is of no significance with regard to their effects on RCBF.

Animals↗

Effects of mannitol and iohexol infusions on the renal cortical blood flow in dehydrated mice.

In vivo fluorescence microscopy was used in experimental studies of renal cortical microcirculation in mice. The effects of intravenous infusions of equimolar concentrations of mannitol and iohexol were studied in normal lean mice and obese/hyperglycemic mice after dehydration overnight. All infusions produced marked effects in distribution and velocity of renal cortical blood flow. Initially increased blood flow was seen in a number of capillaries after infusion of both mannitol and iohexol, and renal cortical blood flow was inhomogeneous for different capillaries. A significantly (p < 0.05) larger number of capillaries with decreased blood flow, within the first minutes after start of infusion, was observed after infusion of iohexol to normal mice when the animals had been dehydrated overnight. Our results indicate that the minor adverse effects on renal cortical blood flow caused by the infusion of contrast medium are potentiated by dehydration.

Animals↗

Functional aspects of mouse islets transplanted to the kidney.

To test whether the transplantation of pancreatic islets affects their basic functions, collagenase-isolated mouse islets were inserted under the left renal capsule of recipient animals. After various periods of time, grafts were removed from the kidney and examined for insulin content and secretory dynamics in a perifusion system. During syngeneic (C57BL/6, BALB/c) or subsyngeneic (NMRI) intrastrain transplantation, the graft insulin content fell drastically during the first week and stayed low for at least 6 weeks; first-phase secretion in general appeared suppressed. Immunosuppression by cyclosporin A had little effect on (sub)syngeneic grafts but markedly improved the performance of allotransplants. Daily injections of the calcium antagonist, verapamil, enhanced the insulin secretory responses of isolated grafts, whether (sub)syngeneic or allogeneic. In syngeneic and subsyngeneic grafts, the potentiating effect of acetylcholine on glucose-induced insulin release was markedly diminished, whereas that of caffeine was not. Transplanted islets also exhibited a subnormal responsiveness to the inhibiting action of noradrenaline. It is concluded that chronic denervation and transplantation of pancreatic islets may cause fundamental changes in the beta-cell responses to physiological regulators of insulin release.

Animals↗

In vivo fluorescence microscopy of microcirculation in the renal cortex of mice. Part V. Effects of mannitol and iohexol infusions in normal, obese/hyperglycemic and diabetic mice.

In vivo fluorescence microscopy was used in experimental studies of renal cortical microcirculation in mice. The effects of i.v. infusions of mannitol and iohexol were studied in normal and obese/hyperglycemic mice and in mice with streptozotocin-induced diabetes mellitus. All infusions produced marked effects on the distribution and velocity of cortical blood flow with no differences between iohexol and mannitol. The renal cortical blood flow was inhomogeneous regarding different capillaries and there was an initial rise in the number of capillaries with increased blood flow after infusions of both mannitol and iohexol. The infusions of contrast medium were initially followed by a significantly larger number of capillaries with decreased blood flow in the obese/hyperglycemic mice (p < 0.05) than in the diabetic and nondiabetic mice. The variations in obese/hyperglycemic groups were, however, large. The effects were the same in normal and diabetic animals.

Animals↗

The protective effect of verapamil on mouse islets transplanted under the kidney capsule.

Islets from normal NMRI mice were transplanted under the kidney capsule of syngeneic recipients. The graft-bearing mice were divided into 4 groups treated daily with cremophor alone (control), cyclosporine (25 mg/kg body wt), CsA in combination with the calcium antagonist verapamil (0.4 mg/kg), or verapamil alone. After 3 weeks the grafts were removed, analyzed for insulin secretory dynamics in a perifusion system, and extracted for their contents of insulin. The graft insulin content was significantly decreased by CsA, an effect counteracted by verapamil. As compared with controls, all treatments increased the basal insulin at 2.8 mmol/L glucose. CsA together with verapamil enhanced the biphasic secretory response to 16.7 mmol/L glucose, whether expressed per graft or per unit of insulin content. The glucose-stimulated insulin release per graft was greater after combining CsA with verapamil than after CsA alone. It is concluded that CsA has adverse effects on islets transplanted to the kidney, and that these effects can be ameliorated by combining the immunosuppressant with verapamil.

Animals↗

Effects of cyclosporin A and verapamil on mouse pancreatic islets.

Treatment of NMRI mice with cyclosporin A (25 mg/kg body wt) for 11 days caused a marked fall in pancreas insulin content, although plasma glucose and plasma insulin were unchanged. When islets from untreated mice were exposed to cyclosporin A (2 mg/l) in vitro, no effect was seen in the first hour. After 24 h, cyclosporin A had significantly decreased the islet content of insulin. Post-culture microperifusion showed that cyclosporin A for 24 or 72 h inhibited the insulin secretory responsiveness. Verapamil in vivo (0.4 mg/kg body wt per day) or in vitro (37.5 micrograms/l) did not modify these effects. Verapamil at 25 mg/l suppressed the release of insulin but afforded no obvious protection against cyclosporin A during culture. The beneficial action of verapamil on islets transplanted to the kidney may reflect renal events rather than a primary interaction of drugs in the islets.

Animals↗

In vivo fluorescence microscopy of microcirculation in the renal cortex of mice. Part III. Effects of mannitol and iohexol infusions after pretreatment with cyclosporin A.

In vivo fluorescence microscopy was used for experimental studies of the renal cortical microcirculation in normal mice and in mice pretreated with the nephrotoxic drug cyclosporin A. The cortical circulation was studied after i.v. infusions of a nonionic low osmolar contrast medium (iohexol) and after infusions of mannitol. All infusions produced marked effects on the distribution and velocity of cortical blood flow with no differences between iohexol and mannitol. The renal cortical blood flow was inhomogeneous regarding different capillaries and there was an initial rise in the number of capillaries with increased blood flow after infusions of both mannitol and iohexol. There was simultaneously an increased number of capillaries with decreased blood flow following all infusions. The decreased blood flow after infusion of iohexol was more pronounced when the animals had been pretreated with cyclosporin A. The difference was only significant (p < 0.05) during a short part of the observation period of 30 min, but it may indicate that kidneys previously exposed to cyclosporin A are more susceptible to infusions of iohexol.

Animals↗

In vivo fluorescence microscopy of microcirculation in the renal cortex of mice. Part IV. Effects of mannitol and iohexol infusions after temporary renal ischemia.

In vivo fluorescence microscopy was used for experimental studies of the renal cortical microcirculation in mice. The effects of i.v. infusions of mannitol and iohexol were studied in untreated mice as well as in mice after temporary renal ischemia. All infusions produced marked effects on the distribution and velocity of cortical blood flow with no differences between iohexol and mannitol. The renal cortical blood flow was inhomogeneous with respect to different capillaries and there was an initial rise in the number of capillaries with increased blood flow after infusions of both mannitol and iohexol. There was an initial increase in the number of capillaries with a decreased blood flow following 30 min of ischemia. This increase was reduced by both types of infusions, suggesting a beneficial effect on renal cortical blood flow. Neither mannitol nor contrast medium exhibited any adverse effects in ischemic kidneys that would be likely to affect renal function. However, 5 min after the infusions there was an increasing number of capillaries with decreased blood flow in all groups.

Animals↗

In vivo fluorescence microscopy of microcirculation in the renal cortex of mice. Part I. An experimental model for contrast media studies.

An experimental model using in vivo fluorescence microscopy for studies of renal cortical blood flow was tested in 40 mice. The model was suitable for testing a wide variety of hypotheses concerning alterations in renal cortical blood flow, including the possibility of inhomogeneous capillary blood flow distribution in response to i.v. infusions. The experimental model was tested for the effects of i.v. infusion of mannitol (0.3 mol/l). Effects of anesthesia and mechanical kidney fixation on renal cortical blood flow were studied. Neuroleptic analgesia was less hazardous to the animals than pentobarbital. Due to artifacts from respiratory and peristaltic motion, it was not possible to use neuroleptic analgesia without mechanical kidney fixation. A rating scale was designed for evaluating the capillary blood flow. The correlation between repeated ratings by the same observer was 0.806 and between 2 different observers 0.59.

Anesthesia↗

In vivo fluorescence microscopy of microcirculation in the renal cortex of mice. Part II. Effects of mannitol and contrast media infusions.

In vivo fluorescence microscopy was used for experimental studies of renal cortical microcirculation in 46 mice. The cortical circulation was studied after i.v. infusions of mannitol of various osmolalities as well as nonionic low osmolar (iohexol) and ionic high osmolar (metrizoate) contrast media. All infusions produced an increase in the number of capillaries with increased blood flow, significantly more pronounced after the infusion of iohexol, metrizoate and mannitol 1.46 mol/l than after the infusion of mannitol 0.3 mol/l. However, the renal cortical blood flow was inhomogeneous with respect to different capillaries. While the blood flow was increased in some capillaries it was to some extent simultaneously decreased in others, significantly more after infusion of metrizoate than after infusion of mannitol 0.3 mol/l.

Animals↗