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Biomedical subjects

M Novak

Publications and source records attributed to M Novak.

At least 55 records · Page 3Linked to original sources
PubMed1988

Studies of high-dose megestrol acetate: potential applications in cachexia.

Cachexia can be a severe problem in the management of patients with cancer and other illnesses because it produces an ever-increasing spiral of anorexia, undernutrition, loss of tissue mass, muscle wasting, and increased susceptibility to infection and treatment toxicity. Megestrol acetate has been observed to produce weight gain in patients with hormone-sensitive tumors and has recently been noted to produce a similar degree of weight gain in those with hormone insensitive tumors. A review of our experience in a phase I-II study of escalating doses of megestrol acetate for advanced breast cancer revealed that weight gain occurred in more than 80% of all treated patients and in 90% of those patients who received treatment for 6 or more weeks. The median maximum weight gain was 5.5 kg, with a range of -5.6 to 44 kg. Subjective improvement in appetite occurred in most patients. These data provided the impetus for a series of further studies of the role of megestrol acetate in the control of cachexia, including a randomized study in cancer cachexia, AIDS cachexia, and anorexia nervosa. In addition, a number of laboratory trials seeking the mechanism of action have been initiated, as well as whole-animal studies to define the compartment of increased weight. Our data and the preliminary observation of weight gain in patients with hormone insensitive tumors suggest that megestrol acetate has a potential role in producing a possibly dose-related subjective improvement and an increase in appetite and weight. Further research is necessary to understand the mechanism of appetite stimulation and anabolic effect.

Body Weight↗
PubMed1988

Mast cell responses to Hymenolepis microstoma infection in mice.

Murine mast cells (MC) responded strongly to Hymenolepis microstoma infection. Starting day 7 postinfection (PI) and continuing until the end of the experiment (35 days PI), significantly larger numbers of MC were present in both the duodenum and bile duct of infected mice than in uninfected controls. In animals challenged with 5 cysticercoids 2 wk after primary infection, the MC response in the duodenum, but not in the bile duct, was of even greater degree than in naive hosts. The majority of MC in the duodenum of infected and challenged mice were intraepithelial mucosal MC, whereas in the bile duct the majority were connective tissue MC. Hypertrophy of the duodenal submucosa and of the bile duct wall was noticeable in all infected and challenged hosts. Worms in primary infections were not affected by the host response, but none of the worms in the challenge dose became established. It is postulated that the type of MC involved in specific immune response of the host is the intraepithelial MC, whereas the cell type participating in general inflammatory events is the connective tissue MC.

Animals↗
PubMed1987

The effects of cross-fostering on the development of social preferences in meadow voles (Microtus pennsylvanicus).

To determine the role of the parental environment in the formation of species attachments in the meadow vole (Microtus pennsylvanicus), young of this species were fostered to either meadow vole parents (in-fostered young) or to prairie vole parents (M. ochrogaster; cross-fostered young). At 50 to 60 days of age, subjects were tested for social preference in an environment that simulated the conditions of a runway system. The testing design assessed the reaction of fostered animals to a novel species (M. pinetorum) as well as to the parental and biological species. The proportion of total test time spent near stimulus animals did not vary as a function of rearing condition. However, when compared to in-fostered controls, cross-fostered meadow voles displayed increased preference for prairie voles. Novelty did not appear to be a significant factor in test animal choice. These results suggest that in meadow voles, preference for the species of social partner is dependent on postnatal experience with parents.

Animals↗
PubMed1987

Examination of the clonal deletion hypothesis following transfusions in rat cardiac transplants.

To test the clonal deletion hypothesis, different levels of immunization were carried out by 0, 1, 2, or 3 transfusions preoperatively, together with 10 methods of immunosuppression. In this way, it was hoped that we could determine the optimal way to immunize and the optimal immunosuppressant treatment to deactivate the responding cells. With the Buffalo-to-Lewis rat heart allograft model, the control mean survival rate was 7 days. Rats with 2 or 3 transfusions had 5- and 12-day survival rates, respectively. If azathioprine was given in addition before grafting, 19- and 18-day survival rates were seen, and if azathioprine was given after grafting, extended survivals of 33 and 34 days were achieved. The longest survival rate of greater than 52 days was obtained by a single transfusion and 25 mg/kg/day of cyclophosphamide given before transplantation. Splenectomy following 2 or 3 transfusions prolonged survival rates to 16-18 days, suggesting that mechanical removal of immunized cells is somewhat effective. Most of the antibody produced by one transfusion was IgM, as were antibodies that resulted from transfusions followed by azathioprine. It is possible that reduction of IgG-producing cells is important. These results are consistent with the clonal deletion theory, although they do not necessarily provide final proof. The experiments suggest that the optimal transfusion effect may be obtained with minimal immunization (1 transfusion) and proper immunosuppression before transplantation.

Animals↗
PubMed1987

Renal wasting of magnesium and phosphate.

We report an asymptomatic man found to have simultaneous renal transport defects for magnesium and phosphate. Associated findings include gout, high frequency hearing loss, chronic elevations of SGOT and SGPT, metabolic bone disease, and hyperparathyroidism. The clinical expression of hyperparathyroidism was masked for 5 years by hypomagnesemia, and the patient became hypercalcemic only when magnesium levels were normalized by intravenous infusion. Both the phosphate and magnesium transport abnormalities persisted after parathyroidectomy. The many unique features of this case distinguish it from previously described disorders of magnesium or phosphate wasting.

Adult↗
PubMed1986

Adult-onset amenorrhea: a study of 262 patients.

A series of 262 patients with amenorrhea of adult onset are reported. Hypothalamic suppression followed by inappropriate positive feedback, and then hyperprolactinemia and ovarian failure are the most frequently encountered etiologies. Other etiologies are diverse and numerically less frequent. Amenorrhea after use of oral contraceptives, or postpill amenorrhea, occurred in 77 (29%) of all patients. The average age of presentation, prior menstrual history, associated morbidity, and subsequent reproductive potential of each diagnostic group are reported. Adult-onset amenorrhea has a less significant impact on future wellbeing than was reported for a similar-sized group of patients whose amenorrhea developed as a result of pubertal aberrancy.

Adult↗
PubMed1986

Hymenolepis diminuta: nuclear magnetic resonance analysis of the excretory products resulting from the metabolism of D-[13C6]glucose.

Excretory products of the tapeworm Hymenolepis diminuta, fed D-[13C6]glucose in vitro for 90 min, were studied using 1H and 13C nuclear magnetic resonance spectroscopy. Signals due to lactate, succinate, acetate, and alanine were identified in the spectra. Several differently labeled species were present for these metabolites; the variations of higher concentration were a consequence of metabolic factors while those of lower concentration could be accounted for by residual 12C in the glucose. The two major labeled lactates, U-13C and 2,3-13C2, were in the ratio 2:1, respectively, and the three major labeled succinates, 1,2,2'-13C3,2,2'-13C2, and U-13C, were present in the ratio 20:10:3, respectively. The different species of labeled end products are related to the overall glucose metabolism of H. diminuta.

Acetates↗
PubMed1986

Detection of N-acetyl-p-benzoquinone imine produced during the hydrolysis of the model phenacetin metabolite N-(pivaloyloxy)phenacetin.

N-Acetyl-p-benzoquinone imine (4) can be detected by UV spectrophotometry and HPLC during the hydrolysis of N-(pivaloyloxy)phenacetin (3c). This material serves as a model for the sulfate and glucuronide conjugates (3a and 3b) of N-hydroxyphenacetin (2). Direct detection of 4 during the hydrolysis of 3a and 3b is precluded by the extreme instability of 3a and the very slow hydrolysis of 3b. Our data show that greater than 90% of the hydrolysis of 3c proceeds through the intermediate 4 at all pH values in the range 1.0-8.0. All our results indicate that 4 is produced through a nitrenium ion mechanism. Many of the differences in the hydrolysis reactions of 3b and 3c can be explained in terms of a mechanism involving tight and solvent-separated nitrenium ion pairs. Other differences may be due to a homolysis pathway, which is more important for the material with the poorer leaving group (3b).

Benzoquinones↗
PubMed1985

Comparison of the effects of imidazo[1,2-a]pyridine-2-carbamates and benzimidazole-2-carbamates on the development of Hymenolepis nana in Tribolium confusum.

The anthelmintic properties of several imidazo[1,2-a]pyridine carbamates and benzimidazole carbamates against Hymenolepis nana are compared. The results of this study, coupled with previous work, indicate that methyl 6-(trichloroethenyl)-imidazo[1,2-a]pyridine-2-carbamate has the potential of being a broad spectrum anthelmintic effective against both nematodes and cestodes.

Animals↗
PubMed1985

Transfer and metabolism of carnitine and carnitine esters in the in vitro perfused human placenta.

The transfer and metabolism of L-carnitine, L-acetylcarnitine, and L-palmitoylcarnitine were studied in the human placenta at term by means of in vitro dual perfusion of a placental lobe. L-Carnitine transfer was 20% that of the freely diffusing antipyrine and 40% that of L-lysine. The transfer of L-acetylcarnitine was similar to that of L-carnitine, but no placental transfer of L-palmitoylcarnitine was found. In contrast to L-lysine, L-carnitine, and L-acetylcarnitine were not actively transported from the maternal to the fetal circulation. No stereospecific transfer of carnitine across the placenta was found. However, there was stereospecific uptake of carnitine by placental tissue. The placenta exhibited an active carnitine metabolism by esterifying free carnitine and hydrolyzing carnitine esters taken up from the perfusion medium and releasing the metabolites into the fetal and maternal circulations.

Acetylcarnitine↗
PubMed1985

How important are carnitine and ketones for the newborn infant?

The newborn oxidizes a large amount of fat. This is reflected in the slow rise of plasma levels of ketones and of total carnitines and acylcarnitines. Feeding a diet devoid of carnitine (soy-based formulas, total parenteral nutrition [TPN] ) rapidly results in a fall in plasma total carnitine levels, whereas in the adult such a fall is observed only after a prolonged time of TPN. This suggests that carnitine synthesis in the newborn is less efficient than in the adult. Gluteal adipocytes in the newborn show a rise in carnitine content and in the activity of carnitine transferases soon after birth, when values are higher than in the adult. Their respiration, lipolysis, and triglyceride formation are enhanced by L-carnitine and inhibited by D-carnitine. This is not so in the adult. Addition of L-carnitine to soybean-based formulas decreases plasma triglyceride and free fatty acid levels in premature infants, who have lower carnitine levels at birth than full-term babies. In pregnant women plasma total carnitine levels are significantly depressed. maternal urinary excretion of total carnitine decreases as gestational age increases, and less is also found in amniotic fluid. Plasma levels of total carnitines and acylcarnitine are the same (or higher) in fetal as in maternal plasma. It is concluded that carnitine may be of particular importance to the neonate and that adding it to foods lacking this substance may be advantageous.

Adipose Tissue↗
PubMed1985

Effects of environmental temperature, sex, and infection with Hymenolepis microstoma on the liver and bile duct weights of mice.

Liver weight of mice was significantly influenced, in order of decreasing prominence, by environmental temperature, infection with Hymenolepis microstoma and sex. Livers of infected and uninfected mice (both sexes) maintained at 5 C for 20 days were proportionally larger (alpha less than or equal to 0.05) than those from corresponding groups of mice kept at 35 C and, except for uninfected males, at 21 C. regardless of temperature, H. microstoma (single-worm infections) produced significant (alpha less than or equal to 0.05) hepatomegaly in all groups of female mice, but, in males, this occurred only in mice maintained at 5 C. At 21 C male mice had proportionally larger livers (alpha less than or equal to 0.05) than corresponding groups of females, but this sexual difference disappeared when mice were maintained at 5 or 35 C. Temperature and sex had a slight but significant effect on bile duct weight. Infection, on the other hand, produced a marked increase in the weight of this organ in both sexes at 5, 21 and 35 C.

Animals↗