Gestational Weight Gain Influences the Adipokine-Oxidative Stress Association during Pregnancy

Introduction and ObjectiveThe weight gained during pregnancy could determine the immediate and future health of the mother-child dyad. Excessive gestational weight gain (EGWG) due to abnormal adipose tissue (AT) accumulation is strongly associated with adverse perinatal outcomes as gestational diabetes, macrosomia, obesity, and hypertension further in life. Dysregulation of adipokine, AT dysfunction, and an imbalance in the prooxidant-antioxidant systems are critical features in altered AT accumulation. This study was aimed to investigate the association between adipokines and oxidative stress markers in pregnant women and the influence of the GWG on this association.MethodsMaternal blood samples were obtained in the third trimester of pregnancy (n = 74) and serum adipokines (adiponectin, leptin, and resistin), oxidative damage markers: 8-oxo-2′-deoxyguanosine (8-oxodG), lipohydroperoxides (LOOH), malondialdehyde (MDA), and carbonylated proteins (CP), and glucose a metabolic marker were measured.ResultsWomen with EGWG had low adiponectin levels than women with adequate weight gain (AWG) or insufficient weight gain (IWG). Multiple linear regression models revealed a positive association between adiponectin and 8-oxodG in women with AWG (B = 1.09, 95% CI: 164–222, p = 0.027) and IWG (B = 0.860, 95% CI: 0.199–1.52, p = 0.013) but not in women with EGWG. In women with EGWG, leptin was positively associated with LOOH (p = 0.018), MDA (p = 0.005), and CP (p = 0.010) oxidative markers.ConclusionOur findings suggest that concurrent mechanisms regulate adipokine production and oxidative stress in pregnant women and that this regulation is influenced by GWG, probably due to an excessive AT accumulation.     

Neural blockade in basal and postreceptor-stimulated intestinal transport

Postreceptor protein stimulation significantly alters the transport state of the ex vivo small intestine. This study investigated the effects of neural blockade on basal and stimulated ionic transport. Rabbit ileal segments (n = 46) were arterially perfused with an oxygenated sanguinous buffered electrolyte solution. The lumen was perfused with an isotonic solution containing [14C]polyethylene glycol as a nonabsorbable marker. Net fluxes of H2O, Na+, and Cl- were calculated. Tetrodotoxin (TTX) was used to block enteric neural transmission. Forskolin (FOR) was used to activate adenylate cyclase, and phorbol 12,13-dibutyrate (PDB) served to activate protein kinase C. Two groups were studied. Group A preparations had no TTX pretreatment, while group B preparations were pretreated with TTX. In the Group A preparations, TTX at 10(-6) M and PDB at 10(-5) M caused significant proabsorptive effects with a delta FH2O of +20 +/- 7 and +15 +/- 2 microliters/min, respectively (P less than 0.05), while FOR stimulated significant secretion with a delta FH2O of -14 +/- 3 microliter/min (P less than 0.05). In the Group B TTX-pretreated preparations, FOR did not cause secretion and PDB maintained an absorptive state. These results indicate that neural blockade with TTX reverses basal secretion in the ex vivo intestine, suggesting that an intact enteric nervous system maintains the secretory status of the intestine. FOR-induced adenylate cyclase-activated secretion does not occur in the presence of TTX, implying that intact neural transmission is required for the FOR effect. PDB-induced protein kinase C-activated absorption occurs despite neural blockade, suggesting that the PDB-induced proabsorptive effect is mediated without neural intermediaries.     

GIANT GASTRIC ULCERS IN CHRONIC SPINAL CORD INJURY PATIENTS

Gastric ulcers cause significant morbidity and mortality to patients with spinal cord injuries. Case reports of three patients with gastric ulcers and chronic spinal cord injuries. Review of the medical literature using MEDLINE ranging from 1975 to 2004. We describe three cases of severe, complicated gastric ulcers in this population. Two cases involve gastric ulcers that eroded into major mesenteric arteries, leading to one fatality. One of these cases revealed a gastric ulcer that looked like a mass because of intralumenal herniation of serosal fat. Diagnosis of ulcer disease is challenging in this patient population as they often do not endorse focal symptoms. Gastroenterologists and other practitioners evaluating chronic spinal cord injury patients should be aware of the potential for giant gastric ulcers, even with benign clinical presentations.     

The effect of calcium on gallbladder absorption

The absorption of water and electrolytes is an important physiologic function of the gallbladder which is altered during gallstone formation. Extracellular calcium and calcium channel antagonists are known to affect intestinal absorption, yet their effect on gallbladder absorption is less well defined. We, therefore, tested the hypothesis that changes in extracellular calcium or in calcium channels would alter gallbladder absorption. New Zealand white rabbit gallbladders were removed, filled with a modified Krebs buffer (Ca2+ = 0.7 mM), and suspended in an oxygenated bath of the same buffer. Water absorption was determined gravimetrically by obtaining serial gallbladder weights at 10-min intervals. After a 40-min control period, the serosal bathing solution was changed to one of four experimental solutions (n = 6 for each group): Ca2+ = 0.25, 0.7, or 1.2 mM or Ca2+ = 0.7 mM plus 0.1 mM verapamil. Absorption was determined during an 80-min experimental period with results expressed as the percentage change in gallbladder absorption compared to that of the control period. The 0.25, 0.7, and 1.2 mM Ca2+ groups did not show a significant change in absorption rate from their respective control rates. However, the verapamil group did demonstrate a significant (P less than 0.05) decrease in absorption rate of -69 +/- 8% by the end of the experimental period. These data demonstrate that verapamil inhibits gallbladder absorption while changes in serosal calcium concentration have no effect. We conclude that calcium channels and intracellular calcium may play an important role in modulating gallbladder absorption.     

Case report: Myxoma of the temporalis muscle

Intramuscular myxomas of the head and neck are rare entities. Primarily found in the myocardium, these lesions also affect the bones and soft tissues. We present a case of an intramuscular myxoma of the temporalis muscle. After reviewing the literature, this case constitutes, to our knowledge, the second reported occurrence of a myxoma in this specific location. The patient was treated for this condition with an excisional biopsy after fine needle aspiration revealed a benign process. No recurrence was seen 18 months after the excision.     

Anti-hepatitis A virus immunoglobulin M antibodies in urine samples for rapid diagnosis of outbreaks

The main goal of this study was to test the feasibility of using urine for diagnosing hepatitis A virus (HAV) infections. A correlation of 90.78% between the test results of urine and serum samples was obtained. Four outbreaks of hepatitis A were confirmed by testing only urine samples. The levels of anti-HAV immunoglobulin M (IgM) antibodies in urine samples remained stable during 6 months of storage at -70 degrees C but decreased when the samples were stored at 4 degrees C. The results of tests of samples obtained 2 and 6 months after infection suggested that IgM levels decline more rapidly in urine than in serum.     

Radiolabeled monoclonal antibodies specific to the extracellular domain of prostate-specific membrane antigen: preclinical studies in nude mice bearing LNCaP human prostate tumor.

Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein, is highly expressed by virtually all prostate cancers. PSMA is also expressed on the tumor vascular endothelium of virtually all solid carcinomas and sarcomas but not on normal vascular endothelium. PSMA is currently the focus of several diagnostic and therapeutic strategies. We have previously reported on the radiolabeling and in vitro binding properties of monoclonal antibodies (mAbs) (J415, J533, and J591) that recognize and bind with high affinity to the extracellular domain of PSMA (PSMA(ext)). This article reports on the in vivo behavior and tumor uptake of (131)I- and (111)In-labeled antiPSMA(ext) mAbs (J415, J533, and J591) and their potential utility for radioimmunotherapy. METHODS: In nude mice bearing PSMA-positive human LNCaP tumors, the pharmacokinetics, biodistribution, and tumor uptake of these antibodies was compared with (111)In-7E11 mAb, specific to the intracellular domain of PSMA (PSMA(int)). Autoradiographic studies were done to identify intratumoral distribution of radiolabeled mAbs. RESULTS: With (131)I-labeled antibodies, the net tumor retention of radioactivity by day 6 was significantly higher with J415 (15.4% +/- 1.1%) and 7E11 (14.5% +/- 1.7%) than with J591 (9.58% +/- 1.1%). By contrast, the tumor uptake of (111)In-1,4,7,10-tetraazacyclododecane-N,N',N", N"'-tetraacetic acid-labeled J415 and J591 gradually increased with time and was quite similar to that of 7E11. In addition, the blood clearance of (111)In-labeled J415 and J591 antibodies was relatively faster than that of radiolabeled 7E11. As a consequence, the tumor-to-blood ratios with J415 and J591 were higher than that of 7E11. The localization of radiolabeled anti-PSMA(ext) antibodies in PSMA-positive LNCaP tumors was highly specific because the tumor uptake of (131)I-labeled J415 and J591 was more than twice that of a nonspecific antibody. Furthermore, the tumor uptake of (131)I-J591 was almost 20 times higher in PSMA-positive LNCaP tumors than in PSMA-negative PC3 and DU145 tumor xenografts. Autoradiographic studies suggested that 7E11 (anti-PSMA(int)) distinctly favors localization to areas of necrosis whereas J415 and J591 (anti-PSMA(ext)) demonstrated a distinct preferential accumulation in areas of viable tumor. CONCLUSION: These results clearly demonstrate that PSMA-specific internalizing antibodies such as J415 and J591 may be the ideal mAbs for the development of novel therapeutic methods to target the delivery of beta-emitting radionuclides ((131)I, (90)Y, and (177)Lu) for the treatment of PSMA-positive tumors. In addition, because J591 and J415 mAbs are specific to PSMA(ext), thus targeting viable tumor, these immunoconjugates are better candidates for targeted radioimmunotherapy than are antibodies targeting PSMA(int).     

Instant nutritional assessment

Instant nutritional assessment of the hospitalized patient is described based upon admission serum albumin levels and total lymphocyte counts. Abnormalities of these parameters are associated with markedly increased morbidity and mortality in a series of 500 consecutively admitted patient. It is suggested that instant nutritional assessment be performed on all hospitalized patients with appropriate alterations and therapy being made to allow for nutritional repletion.     

Small-bowel origin of the signal for meal-induced jejunal absorption

A meal stimulates the absorption of water and electrolytes from the proximal jejunal lumen. Neither sham feeding nor gastric distention alters this meal-induced jejunal absorption, implying no role for the cephalic or gastric phases of digestion. This study tested the hypothesis that the small bowel is the origin of the proabsorptive signal for meal-induced jejunal absorption. Twenty-five-centimeter canine proximal jejunal Thiry-Vella fistulas were constructed, and chronic duodenal catheters were placed. Jejunal absorption studies (n = 72) were performed by luminal perfusion of the jejunal segments with an isotonic buffer containing radioactive carbon-labeled polyethylene glycol. Each study consisted of a 1-hour basal period followed by a 3-hour experimental period. Ten groups were studied: control, orally ingested mixed meal, and 600 ml duodenal infusions of either water, saline solution, protein, lipid, carbohydrate, 150 mmol/L mannitol, 300 mmol/L mannitol, or 600 mmol/L mannitol, each delivered at 10 ml/min over 60 minutes. The control, water, and saline solution groups showed no significant changes in integrated 3-hour jejunal absorption above basal. The ingested mixed meal significantly increased water and electrolyte absorption (p less than 0.0001). The isovolumetric, isocaloric duodenal nutrient infusions of protein, lipid, and carbohydrate all significantly increased jejunal water and electrolyte absorption (p less than 0.0001). The poorly absorbed solute mannitol significantly increased absorption (p less than 0.0001) in a dose-dependent fashion. These results indicate that the proabsorptive signal for meal-induced jejunal absorption originates from or distal to the duodenum. This newly defined enteroenteric response occurs independently of nutrient composition and responds to increasing osmolarity of poorly absorbed solutes such as mannitol.