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Influence of nutrient restriction and melatonin supplementation of pregnant ewes on maternal and fetal pancreatic digestive enzymes and insulin-containing clusters
- F. E. Keomanivong, C. O. Lemley, L. E. Camacho, R. Yunusova, P. P. Borowicz, J. S. Caton, A. M. Meyer, K. A. Vonnahme, K. C. Swanson
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Primiparous ewes (n=32) were assigned to dietary treatments in a 2×2 factorial arrangement to determine effects of nutrient restriction and melatonin supplementation on maternal and fetal pancreatic weight, digestive enzyme activity, concentration of insulin-containing clusters and plasma insulin concentrations. Treatments consisted of nutrient intake with 60% (RES) or 100% (ADQ) of requirements and melatonin supplementation at 0 (CON) or 5 mg/day (MEL). Treatments began on day 50 of gestation and continued until day 130. On day 130, blood was collected under general anesthesia from the uterine artery, uterine vein, umbilical artery and umbilical vein for plasma insulin analysis. Ewes were then euthanized and the pancreas removed from the ewe and fetus, trimmed of mesentery and fat, weighed and snap-frozen until enzyme analysis. In addition, samples of pancreatic tissue were fixed in 10% formalin solution for histological examination including quantitative characterization of size and distribution of insulin-containing cell clusters. Nutrient restriction decreased (P⩽0.001) maternal pancreatic mass (g) and α-amylase activity (U/g, kU/pancreas, U/kg BW). Ewes supplemented with melatonin had increased pancreatic mass (P=0.03) and α-amylase content (kU/pancreas and U/kg BW). Melatonin supplementation decreased (P=0.002) maternal pancreatic insulin-positive tissue area (relative to section of tissue), and size of the largest insulin-containing cell cluster (P=0.04). Nutrient restriction decreased pancreatic insulin-positive tissue area (P=0.03) and percent of large (32 001 to 512 000 µm2) and giant (⩾512 001 µm2) insulin-containing cell clusters (P=0.04) in the fetus. Insulin concentrations in plasma from the uterine vein, umbilical artery and umbilical vein were greater (P⩽0.01) in animals receiving 100% requirements. When comparing ewes to fetuses, ewes had a greater percentage of medium insulin-containing cell clusters (2001 to 32 000 µm2) while fetuses had more (P<0.001) pancreatic insulin-positive area (relative to section of tissue) and a greater percent of small, large and giant insulin-containing cell clusters (P⩽0.02). Larger insulin-containing clusters were observed in fetuses (P<0.001) compared with ewes. In summary, the maternal pancreas responded to nutrient restriction by decreasing pancreatic weight and activity of digestive enzymes while melatonin supplementation increased α-amylase content. Nutrient restriction decreased the number of pancreatic insulin-containing clusters in fetuses while melatonin supplementation did not influence insulin concentration. This indicated using melatonin as a therapeutic agent to mitigate reduced pancreatic function in the fetus due to maternal nutrient restriction may not be beneficial.
Dietary melatonin supplementation alters uteroplacental amino acid flux during intrauterine growth restriction in ewes
- C. O. Lemley, L. E. Camacho, A. M. Meyer, M. Kapphahn, J. S. Caton, K. A. Vonnahme
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Dietary melatonin supplementation during mid- to late-gestation increased umbilical artery blood flow and caused disproportionate fetal growth. This melatonin-induced increase in umbilical artery blood flow may alter nutrient availability to the fetus, which may lead to alterations in fetal size. The objectives of the current experiment were to determine amino acid (AA) and glucose concentrations as well as AA and glucose flux across the uteroplacenta using a mid- to late-gestation model of intrauterine growth restriction supplemented with dietary melatonin as a 2 × 2 factorial design. At day 50 of gestation, 32 ewes were supplemented with 5 mg of melatonin (MEL) or no melatonin (CON) and were allocated to receive 100% (adequate; ADQ) or 60% (restricted; RES) of nutrient requirements. On day 130 of gestation, uterine and umbilical blood flows were determined via Doppler ultrasonography during a non-survival surgery. Blood samples were collected under general anesthesia from the maternal saphenous artery, gravid uterine vein, umbilical artery, and umbilical vein for AA analysis and glucose. Total α-AA concentrations in maternal artery and gravid uterine vein were decreased (P < 0.05) in RES v. ADQ fed ewes. Maternal arterial − venous difference in total α-AA was increased (P ⩽ 0.01) in RES v. ADQ fed ewes, while total uterine α-AA flux was not different (P > 0.40) across all treatment groups. Fetal venous − arterial difference in total α-AA as well as uteroplacental flux of total α-AA were decreased (P < 0.05) in CON-RES v. CON-ADQ, and similar (P > 0.20) in MEL-RES v. CON-ADQ. Maternal concentrations and uterine flux of branched-chain AA (BCAA) were not different across all treatment groups; however, fetal uptake of BCAA was decreased (P < 0.05) in CON-RES v. CON-ADQ, and similar (P > 0.20) in MEL-RES v. CON-ADQ. Uterine uptake of glucose was not different (P ⩾ 0.08) across all treatment groups, while uteroplacental uptake of glucose was increased (P ⩽ 0.05) in RES v. ADQ ewes. In conclusion, maternal nutrient restriction increased maternal arterial − venous difference in total α-AA, while total uterine α-AA flux was unaffected by maternal nutrient restriction. Melatonin supplementation did not impact maternal serum concentrations or uterine flux of glucose or AA; however, melatonin did improve fetal BCAA uptake during maternal nutrient restriction.
Correlates of codisorders in homeless and never homeless indigent schizophrenic men
- C. L. M. Caton, P. E. Shrout, P. F. Eagle, L. A. Opler, A. Felix
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- Psychological Medicine / Volume 24 / Issue 3 / August 1994
- Published online by Cambridge University Press:
- 09 July 2009, pp. 681-688
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We recently completed a case–control study of 100 literally homeless and 100 never homeless indigent schizophrenic men in New York City, in which concurrent substance abuse and antisocial personality disorder were widespread. In this paper we probe the correlates of ‘pure’ schizophrenia (single disorder, N = 60), schizophrenia and substance abuse (double disorder, N = 89), and schizophrenia, substance abuse, and antisocial personality disorder (triple disorder, N = 50), across the homeless/never homeless distinction. Subjects were recruited from a homeless shelter and mental health service programmes in Upper Manhattan. Psychologist and social worker interviewers administered the Structured Clinical Interview for DSM-III-R, I, and II and other structured instruments to explore social, family and illness history, the current illness, and aspects of treatment and family support. Codisorder subjects emerged from more disadvantaged family backgrounds, experienced greater school difficulties, began drug use in early adolescence, were more prone to hyperactivity in childhood, and were more likely to have spent time in jail. While codisorder groups did not differ on key aspects of schizophrenia, the triple disorder group was found to suffer from a more severe form of substance abuse than double disorder subjects, associated with an earlier age of onset and abuse of a wider array of substances.
The widespread prevalence of codisorders among indigent schizophrenic men has major significance for clinical psychiatry. Study of the correlates of codisorders has revealed important differences in social, family, and illness history which may guide the development of more effective treatments and improved service delivery.