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M Horowitz

Publications and source records attributed to M Horowitz.

At least 91 records · Page 5Linked to original sources

Effect of diet on the response to leptin in the marsupial Sminthopsis crassicaudata.

The aim of this study was to determine in the marsupial Sminthopsis crassicaudata 1) the effect of leptin on food intake, body fat stores, and metabolism and 2) whether leptin can prevent a diet-induced increase in adiposity. In response to 21 days of feeding with mealworms (2.99 kcal/g, 30% fat), body weight (P < 0. 0001) and tail width (P < 0.0001) increased, compared with control animals fed with laboratory diet (1.01 kcal/g, 20% fat). Subsequently, S. crassicaudata were randomly allocated to receive either laboratory diet or a choice between laboratory diet and mealworms. For 13 days, one-half of the animals in each dietary group received intraperitoneal human leptin (2.5 mg/kg twice daily), while the other one-half received phosphate-buffered saline. In animals receiving laboratory diet alone, leptin induced a decrease in body weight (P < 0.0001), tail width (P < 0.0001), and energy intake (P < 0.01). In animals receiving both laboratory diet and mealworms, leptin had no effect on body weight or tail width, although the proportion of laboratory diet eaten was reduced (P = 0. 0001), and there was a nonsignificant fall in overall energy intake (P = 0.07). We conclude that in S. crassicaudata, 1) a high-calorie, higher-fat diet induces an increase in adiposity and 2) leptin induces weight loss, but 3) an increase in dietary calories and fat content is associated with resistance to the actions of leptin.

Animals↗

Heat acclimation induces changes in cardiac mechanical performance: the role of thyroid hormone.

The involvement of reduced thyroxine level in the emergence of heat acclimation-induced negative lusitropic effect was examined. Experiments were carried out on 1) control rat hearts maintained at 24 +/- 1 degreesC (C); 2) rat hearts acclimated at 34 degreesC for 1 mo (AC); 3) AC-euthyroid rat hearts, via administration of thyroxine in the drinking water (AT); and 4) hypothyroid rat hearts, maintained at 24 +/- 1 degreesC, via administration of thiouracil in the drinking water (CP). Systolic pressure and velocities of contraction (dP/dt. P) and relaxation (-dP/dt. P) were measured using the Langendorff perfusion system. The steady-state levels of Ca2+-ATPase and phospholamban mRNAs and the expression of the encoded proteins Ca2+-ATPase (SERCA) and phospholamban (PLB) were measured, using semi-quantitative RT-PCR and Western immunoblotting, respectively. Rat thyroxine levels were measured using RIA. Heat acclimation, which brought about a reduced thyroxine level, led to downregulation of Ca2+-ATPase mRNA expression and translation and upregulation of phospholamban mRNA and PLB. Consequently, the PLB-to-SERCA ratio (PLB/SERCA) of the AC hearts showed a significant increase. These changes, as well as the greater pressure generation and the reduced dP/dt. P and -dP/dt. P observed in AC hearts were blunted in the AT hearts. Our data suggest that sustained heat acclimation-induced low thyroxine level has a decisive effect on the contractile machinery of the AC heart. Elevated PLB/SERCA apparently explains the negative lusitropic effect observed in these hearts.

Acclimatization↗

Heat acclimation increases the basal HSP72 level and alters its production dynamics during heat stress.

It has been previously shown that heat acclimation leads to an elevated basal level of 72-kDa heat shock protein (HSP72). Augmented expression of HSP72 is considered as a cytoprotective response. This led us to hypothesize that alterations in the heat shock protein (HSP) defense pathway are an integral part of the heat acclimation repertoire. To investigate this, we studied the temporal profile of basal HSP expression upon acclimation and the dynamics of their accumulation subsequent to acute heat stress (HS). In parallel, HSP72 mRNA level before and after HS was measured. For comparison, HSC mRNA [the constitutive member of 70-kDa HSP (HSP70) family] was measured in similar conditions. Heat acclimation was attained by continuous exposure of rats to 34 degrees C for 0, 1, 2, and 30 days. HS was attained by exposure to 41 or 43 degrees C for 2 h. Thermoregulatory capacity of the rats was defined by rectal temperature, heating rate, and the cumulative heat strain invoked during HS. HSP72 and HSP70 gene transcripts were measured in the left ventricle of the heart by means of Western immunoblotting and semiquantitative RT-PCR, respectively. The resultant acclimatory change comprised a higher resting level of the encoded 72-kDa protein (Delta175%, P < 0.0001). After HS, peak HSP72 mRNA level was attained, 40 and 20 min post-HS at 41 and 43 degrees C, respectively, vs. 60 and 40 min in the nonacclimated group. The subsequent HSP synthesis, however, was dependent on the severity of the cumulative heat strain. At the initial phase of heat acclimation, augmented HSP72 transcription unaccompanied by HSP synthesis was observed. It is concluded that upon heat acclimation, the HSP defense pathway is predisposed to a faster response. At the initial phases of heat acclimation, inability to elevate the HSP cytosolic level rules out their direct cytoprotective role.

Acclimatization↗

Effect of nitric oxide synthase inhibitors on short-term appetite and food intake in humans.

Animal studies suggest that nitric oxide (NO) may be a physiological regulator of appetite; NO synthase (NOS) inhibition suppresses food intake in rats, mice, and chickens. It is not known whether NO has any effect on appetite in humans. We have used NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME), both competitive, nonselective inhibitors of NOS, in two separate studies to evaluate the role of NO in the short-term regulation of appetite in humans. In study I, 13 men (18-25 yr) underwent paired studies, in randomized, double-blind fashion, after an overnight fast. L-NMMA (4 mg. kg-1. h-1) or saline (0.9%) was infused intravenously at a rate of 40 ml/h for 1.5 h. In study II, eight men (18-26 yr) underwent three randomized, double-blind studies after an overnight fast. L-NAME (75 or 180 micrograms . kg-1. h-1) or saline (0.9%) was infused intravenously at a rate of 20 ml/h for 120 min. Hunger and fullness were measured using visual analog scales; blood pressure and heart rate were monitored, and 30 min before the end of the infusion, subjects were offered a cold buffet meal. Total caloric intake and the macronutrient composition of the meal were determined. Both L-NMMA (P = 0.052) and L-NAME (P < 0.05; both doses) decreased heart rate, L-NMMA increased diastolic blood pressure (P < 0.01), and L-NAME increased systolic blood pressure (P = 0.052). Neither drug had any effect on caloric intake or sensations of hunger or fullness. Despite having significant effects on cardiovascular function in the doses used, neither L-NMMA nor L-NAME had any effect on feeding, suggesting that NO does not affect short-term appetite or food intake in humans.

Adolescent↗

Heat acclimation and hypohydration: involvement of central angiotensin II receptors in thermoregulation.

This investigation attempted to confirm the involvement of central ANG II-ergic signals in thermoregulation. Experiments were conducted on rats undergoing short (STHA)- and long (LTHA)-term heat acclimation, with and without superimposed hypohydration. Vasodilatation (VTsh) and salivation (STsh) temperature thresholds, tail blood flow, and heat endurance were measured in conscious rats during heat stress (40 degrees C) before and after losartan (Los), an ANG II AT(1)-selective receptor antagonist, administration either to the lateral ventricle or intravenously. Heat acclimation alone resulted in decreased VTsh. STsh decreased during STHA and resumed the preacclimation value, together with markedly increased heat endurance on LTHA. Hypohydration did not affect this biphasic response, although STsh was elevated in all groups. The enhanced heat endurance attained by LTHA was blunted. Neither Los treatment affected the nonacclimated rats. In the heat-acclimated, euhydrated rats, intracerebroventricular Los resulted in decreased VTsh, whereas intravenous Los resulted in elevated STsh. Both intracerebroventricular and intravenous Los led to markedly enhanced heat endurance of the LTHA hypohydrated rats. It is concluded that the LTHA group showed a loss of the benefits acquired by acclimation on hypohydration, whereas the STHA rats, which show an accelerated autonomic excitability in that phase, gained some benefit. It is suggested that ANG II modulates thermoregulation in conditions of chronic adjustments. Central ANG II signals may lead to VTsh upshift, whereas circumventricular structures, activated via circulating ANG II, decrease STsh. On hypohydration these responses seem to be desensitized.

Acclimatization↗

Heat stress induces ultrastructural changes in cutaneous capillary wall of heat-acclimated rock pigeon.

In heat-acclimated rock pigeons, cutaneous water evaporation is the major cooling mechanism when exposed at rest to an extremely hot environment of 50-60 degrees C. This evaporative pathway is also activated in room temperature by a beta-adrenergic antagonist (propranolol) or an alpha-adrenergic agonist (clonidine) and inhibited by a beta-adrenergic agonist (isoproterenol). In contrast, neither heat exposure nor drug administration activates cutaneous evaporation in cold-acclimated pigeons. To elucidate the mechanisms underlying this phenomenon, we studied the role of the ultrastructure and permeability of the cutaneous vasculature. During both heat stress and the administration of propranolol and clonidine, we observed increased capillary fenestration and endothelial gaps. Similarly, propranolol increased the extravasation of Evans blue-labeled albumin in the skin tissue. We concluded that heat acclimation reinforces a mechanism by which the activation of adrenergic signal transduction pathways alters microvessel permeability during heat stress. Consequently the flux of plasma proteins and water into the interstitial space is accelerated, providing an interstitial source of water for sustained cutaneous evaporative cooling.

Acclimatization↗

The physiological strain index applied to heat-stressed rats.

A physiological strain index (PSI) based on heart rate (HR) and rectal temperature (Tre) was recently suggested to evaluate exercise-heat stress in humans. The purpose of this study was to adjust PSI for rats and to evaluate this index at different levels of heat acclimation and training. The corrections of HR and Tre to modify the index for rats are as follows: PSI = 5 (Tre t - Tre 0). (41.5 - Tre 0)-1 + 5 (HRt - HR0). (550 - HR0)-1, where HRt and Tre t are simultaneous measurements taken at any time during the exposure and HR0 and Tre 0 are the initial measurements. The adjusted PSI was applied to five groups (n = 11-14 per group) of acclimated rats (control and 2, 5, 10, and 30 days) exposed for 70 min to a hot climate [40 degrees C, 20% relative humidity (RH)]. A separate database representing two groups of acclimated or trained rats was also used and involved 20 min of low-intensity exercise (O2 consumption approximately 50 ml. min-1. kg-1) at three different climates: normothermic (24 degrees C, 40% RH), hot-wet (35 degrees C, 70% RH), and hot-dry (40 degrees C, 20% RH). In normothermia, rats also performed moderate exercise (O2 consumption approximately 60 ml. min-1. kg-1). The adjusted PSI differentiated among acclimation levels and significantly discriminated among all exposures during low-intensity exercise (P < 0.05). Furthermore, this index was able to assess the individual roles played by heat acclimation and exercise training.

Acclimatization↗

Effect of heat acclimation and heat shock on oscillations of carbamyl-choline-evoked Ca2+ signal in HSY cell line.

We studied effects of heat acclimation (HA) and acute heat stress (HS) on Ca2+ signal oscillations following supramaximal carbamyl-choline (CCh) stimulation, using HSY cell line as a model. In the control cells, oscillations decreased their amplitude with time. HS alone did not change either oscillation amplitude or frequency, although calcium release to the cytosol upon CCh stimulation was faster. HA increased maximal oscillation amplitude only. There was no change in basal cytosolic calcium level and peak evoked signal in all experimental conditions. Collectively, the data suggest that HA affects the oscillation profile. Changes in the oscillation profile did not correlate with changes in the resting and evoked Ca2+ signal, which suggests that the oscillations are a separate target for heat acclimation.

Acclimatization↗

Hyperglycemia attenuates the gastrokinetic effect of erythromycin and affects the perception of postprandial hunger in normal subjects.

OBJECTIVE: The major aims of this study were to determine in normal subjects whether the effects of erythromycin on gastric emptying, postprandial hunger, and fullness are modified by the blood glucose concentration. RESEARCH DESIGN AND METHODS: A total of 10 normal subjects (aged 20-39 years) underwent concurrent measurements of gastric emptying, blood glucose, hunger, and fullness on four separate occasions: twice during euglycemia (approximately 4 mmol/l) and twice during hyperglycemia (approximately 15 mmol/l). Either erythromycin (3 mg/kg) or saline (0.9%) was administered intravenously immediately before ingestion of a radioisotopically labeled solid meal. RESULTS: Gastric emptying was slower (P < 0.0001) during hyperglycemia when compared with euglycemia after both erythromycin and saline administration. During hyperglycemia, erythromycin reduced the lag phase (77.8 +/- 12.6 vs. 20.3 +/- 7.3 min; P < 0.05) but had no effect on the postlag emptying rate (0.32 +/- 0.077% per min vs. 0.24% per min). Hunger decreased (P < 0.001) and fullness increased (P < 0.001) after the meal. Postprandial hunger was less during hyperglycemia after saline infusion (P < 0.05) but not after erythromycin. Hunger was greater after erythromycin during both hyperglycemia and euglycemia (P < 0.05). CONCLUSIONS: At a blood glucose concentration of approximately 15 mmol/l, 1) gastric emptying of a solid meal is slower, when compared with euglycemia, even after administration of erythromycin; 2) the effect of erythromycin on gastric emptying of a solid meal is attenuated; and 3) the perception of postprandial hunger is reduced.

Adult↗

Natural history of diabetic gastroparesis.

OBJECTIVE: The major aim of this study was to evaluate the prognosis of diabetic gastroparesis. RESEARCH DESIGN AND METHODS: Between 1984 and 1989, 86 outpatients with diabetes (66 type 1, 20 type 2; 40 male, 46 female) underwent assessment of solid and liquid gastric emptying and esophageal transit (by scintigraphy), gastrointestinal symptoms (by questionnaire), autonomic nerve function (by cardiovascular reflex tests), and glycemic control (by HbAlc and blood glucose concentrations during gastric emptying measurement). These patients were followed up in 1998. RESULTS: Of the 86 patients, solid gastric emptying (percentage of retention at 100 min) was delayed in 48 (56%) patients and liquid emptying (50% emptying time) was delayed in 24 (28%) patients. At follow-up in 1998, 62 patients were known to be alive, 21 had died, and 3 were lost to follow-up. In the group who had died, duration of diabetes (P = 0.048), score for autonomic neuropathy (P = 0.046), and esophageal transit (P = 0.032) were greater than in those patients who were alive, but there were no differences in gastric emptying between the two groups. Of the 83 patients who could be followed up, 32 of the 45 patients (71%) with delayed solid emptying and 18 of the 24 patients (75%) with delay in liquid emptying were alive. After adjustment for the effects of other factors that showed a relationship with the risk of dying, there was no significant relationship between either gastric emptying or esophageal transit and death. CONCLUSIONS: In this relatively large cohort of outpatients with diabetes, there was no evidence that gastroparesis was associated with a poor prognosis.

Adolescent↗

Vesicoureteral reflux in infants with prenatal hydronephrosis confirmed at birth: racial differences.

PURPOSE: We compared the incidence of vesicoureteral reflux in black and nonblack patients in whom prenatal hydronephrosis was confirmed postnatally. MATERIALS AND METHODS: We reviewed the records of 58 black and 51 nonblack patients with confirmed hydronephrosis who underwent voiding cystourethrography. RESULTS: Reflux was present in 9 cases (8.3%). The prevalence of reflux in black and nonblack patients was 0 and 17.6%, respectively. CONCLUSIONS: The absence of vesicoureteral reflux in black infants with prenatal hydronephrosis and the 17.6% incidence in nonblack infants suggest that voiding cystourethrography should not be routinely performed in the black population, although it should continue to be done on a routine basis in the nonblack population.

Black People↗

The effects of season and alcohol intake on mineral metabolism in men.

We have examined the relationship between self-reported alcohol intake (SRAI), season and mineral metabolism in a series of 96 men aged 32 to 78 years of age. Alcohol intake was reported as between 0 and 50 oz/week. SRAI correlated positively with liver function tests, including serum bilirubin, alkaline phosphatase, and AST initially and at 6 months. In addition, SRAI correlated with serum calcium, testosterone, estradiol, and immunoreactive parathyroid hormone (iPTH) as well as urinary calcium [per 100 mg of creatinine (Cr)], and pyridinoline crosslinks (DPC) (per 100 mg of Cr). We have divided the participants into two groups on the basis of their reported alcohol intake. Individuals with none-to-moderate intake had <8.4 oz/week of ethanol. Those with moderate or heavier intake had 8.4 oz or more of ethanol/week. Individuals with none-to-moderate SRAI had a significant seasonal increase in iPTH, osteocalcin, urine DPC/100 mg of Cr and a decrease in distal forearm bone mineral density, 25 hydroxyvitamin D (250HD), and urinary calcium/100 mg of Cr. Individuals with moderate or heavier SRAI only had significant seasonal decrease in 250HD. We have concluded that alcohol intake decreases seasonal change in serum iPTH. The biological effects of such alterations in parathyroid hormone levels include decreased seasonal loss of bone mineral density.

Adult↗

Gastric emptying in diabetes mellitus: relationship to blood-glucose control.

The application of novel investigative techniques has established that disordered gastric motility is a frequent complication of diabetes mellitus. Thus, gastric emptying of solid or nutrient liquid meals is abnormal in 30% to 50% of randomly selected outpatients with long-standing type 1 or type 2 diabetes. Delayed gastric emptying occurs more frequently than rapid emptying. There is increasing evidence that disordered gastric motility has a major impact on the management of patients with diabetes mellitus by leading to gastrointestinal symptoms and poor glycemic control. Although both gastroparesis and upper gastrointestinal symptoms have been attributed to irreversible autonomic damage, it is now clear that acute changes in the blood-glucose concentration have a major effect on both gastrointestinal motor function and the perception of sensations arising in the gut. For example, there is an inverse relationship between the rate of gastric emptying and the blood-glucose concentration, so that gastric emptying is slower during hyperglycemia and accelerated during hypoglycemia. This article reviews some issues in the etiology, diagnosis, and management of problems associated with gastric emptying in elderly persons with diabetes mellitus.

Aged↗

Emotional control theory and the concept of defense: A teaching document.

Defensiveness in intrapsychic and interpersonal activities is a generally accepted concept among psychodynamic theorists, but a theoretically grounded classification of emotional control processes is needed. As a result of intensive case-by-case clinical and empirical studies, such a system was assembled. The system is organized by three major categories of processes that can regulate emotions. These are sets of mental operations that control 1) content of thought and communications, 2) form of thought and communications, and 3) person schemas that organize beliefs and interpersonal expressions. Each category of defensive control processes is linked to observable outcomes at intrapsychic and interpersonal levels. This classification system can be used to formulate how patterns of avoidance and distortion are formed.(The Journal of Psychotherapy Practice and Research 1999; 8:213-224)

Adult↗

The adolescent varicocele I: left testicular hypertrophy following varicocelectomy.

PURPOSE: Ipsilateral testicular catch-up growth has been reported to occur in approximately 80% of adolescents with varicoceles following unilateral varicocelectomy. We have been observing not only catch-up growth, but hypertrophy (left at least 10% larger than right testicular volume) in some adolescents postoperatively. To our knowledge this phenomenon has not been previously described. We assess the incidence of left testicular hypertrophy following ipsilateral varicocele ligation and whether it is related to age at operation and/or procedure performed. MATERIALS AND METHODS: We reviewed the records of 42 patients who underwent unilateral left varicocelectomy for asymptomatic varicoceles. Testicular volume was determined before and after surgery, and all patients were followed for a minimum of 6 months. Indication for surgery was ipsilateral left testicular hypotrophy in 23 cases, grade 2 to 3 varicocele with palpably softer ipsilateral left testicle in 5, grade 3+ varicoceles in 12, an exaggerated response to gonadotropin-releasing hormone stimulation test in 1 and persistent pain in 1. Average patient age at operation was 14.7 years (range 9 to 22) and average followup was 22 months (range 6 to 84). Patients were stratified according to Palomo versus modified Ivanissevich technique and age at operation. Testes were measured using the Takihara ring orchidometer with relative volume of the left testis expressed as a percentage of the right testis. Results were compared in different age groups as well as by procedure performed to correct the varicocele using chi-square analysis. RESULTS: Left testicular hypertrophy developed in 13 of 32 patients (43.8%) who underwent a Palomo repair and in 3 of the 10 (30%) who underwent a modified Ivanissevich repair. When compared by age at operation, 8 of 20 patients (40%) 14.7 years old or younger had left testicular hypertrophy compared to 8 of 22 (36.4%) older than 14.7 years. Differences between these groups were not statistically significant. CONCLUSIONS: Ipsilateral testicular hypertrophy occurs in a substantial number of adolescents following varicocele ligation. This phenomenon does not seem to be dependent on age at surgery or type of varicocele repair.

Adult↗

Dantrolene and recovery from heat stroke.

Several authors have shown that dantrolene may be effective in the treatment of heat stroke patients. However, the scant data available are still controversial. The aim of this investigation was to establish an animal experimental model for studying the efficacy of this drug both as a prophylactic agent and as a means of hastening the cooling process after heat stroke. Male albino rats were divided into five groups: Sedentary controls (SC), Sedentary+dantrolene (S+D), Exercise controls (EC), and Exercise+dantrolene (E+D, E+D1). The drug (140 mg x kg(-1) body weight) was administered i.v. either prior to subjection to heat stress (40 degrees C) (S+D, E+D) or upon development of heat stroke syndrome (E+D1). In the S+D group, dantrolene administered prior to heat stress (HS) delayed the development of heat stroke by 70%, although colonic temperature (Tc) at the onset of heat stroke was similar to that in group SC (43.0 +/- 0.1 degrees C and 43.2 +/- 0.4 degrees C for S+D and SC, respectively). In E+D animals, dantrolene shortened exercise endurance in the heat by 17.5%, but concomitantly hindered severe Tc rise (40.9 +/- 0.2 degrees C and 40.0 +/- 0.2 degrees C for EC and E+D, respectively). Administration of dantrolene on the development of heat stroke appeared to improve cooling in the exercise group (0.25 degrees C x min(-1) and 0.18 degrees C x min(-1), for the first 1 5 min of cooling, for E+D1 and EC, respectively). The results suggest that dantrolene is effective as a prophylactic agent in sedentary animals only. It also might have application on development of heat stroke. It is hypothesized that the observed rapid cooling is associated with dantrolene's effect on muscle contraction, thus leading to attenuated heat production and peripheral vascular relaxation.

Analysis of Variance↗

Nutrition, osteoporosis, and aging.

Loss of bone is an almost universal accompaniment of aging that proceeds at an average rate of 0.5-1% per annum from midlife onwards. There are at least four nutrients involved in this process: calcium, salt, protein, and vitamin D, at least in women. The pathogenesis of osteoporosis in men is more obscure. Calcium is a positive risk factor because calcium requirement rises at the menopause due to an increase in obligatory calcium loss and a small reduction in calcium absorption that persist to the end of life. A metaanalysis of 20 calcium trials shows that this process can generally be arrested by calcium supplementation, although there is some doubt about its effectiveness in the first few years after menopause. Salt is a negative risk factor because it increases obligatory calcium loss; every 100 mmol of sodium takes 1 mmol of calcium out of the body. Restricting salt intake lowers the rate of bone resorption in postmenopausal women. Protein is another negative risk factor; increasing animal protein intake from 40 to 80 g daily increases urine calcium by about 1 mmol/day. Low protein intakes in third world countries may partially protect against osteoporosis. Vitamin D (sometimes called a nutrient and sometimes a hormone) is important because age-related vitamin D deficiency leads to malabsorption of calcium, accelerated bone loss, and increased risk of hip fracture. Vitamin D supplementation has been shown to retard bone loss and reduce hip fracture incidence in elderly women.

Aged↗