Role of third intracellular loop of galanin receptor type 1 in signal transduction

To determine the domains essential for G-protein coupling of the human galanin receptor type 1 (GalR1), we have used both GalR1 mutants and synthetic receptor-derived peptides in(125)I-galanin and [(35)S]-GTPgammaS binding studies. Replacement of potential phosphorylation sites by Leu in the third intracellular loop (IC3) of GalR1 did not affect K(D)values for the receptor. Peptides derived form the IC3 loop, and especially the N-terminal part of it were able to increase the rate of [(35)S]-GTPgammaS binding to the trimeric Gialpha1beta1gamma2, but not to Gsalphabeta1gamma2, whereas the peptides corresponding to the IC1 and IC2 loops had no such effect. IC3 loop peptides also inhibited the binding of(125)I-galanin to GalR1 in membranes from Rin m5F cells. Our results suggest that the IC3 loop of GalR1, especially its N-terminal part, defines the coupling of the receptor to the Gialpha1beta1gamma2 protein and consequently, to the signal transduction cascade.     

Neutrophil chemotaxis and random migration in preterm and term infants with sepsis

The aim of this study was to evaluate neutrophil chemotaxis and random migration in healthy newborn infants and septic neonates with similar gestational and postnatal age. Possible relationships between chemotactic activity, random migration, causative microorganisms, and clinical course of septic infants were also investigated. The neutrophil chemotaxis and random migration was evaluated in 24 healthy newborn babies and 34 septic neonates and 20 healthy adults by modified Boyden technique. The mean neutrophil chemotaxis of healthy preterm-term infants and adults were similar (66.6 +/- 18.9, 64.4 +/- 19.9, and 74.7 +/- 17 microm, respectively). The mean neutrophil random migration of healthy term infants was not different than that of adults. But the mean neutrophil random migration of healthy preterm infants was lower than that of adults (36.9 +/- 13.7 and 43.5 +/- 1 1.8 microm, respectively) (p = 0.03). The mean neutrophil chemotaxis and random migration septic term infants were not different from the value of healthy term infants (p > 0.05). Although the mean random migration of septic and preterm infants were similar (p > 0.05), the mean neutrophil chemotaxis of septic preterm infants was lower than the value of healthy preterm infants (p = 0.04). Not only mean neutrophil chemotaxis of septic preterm and term infants were significantly lower than that of adults (p = 0.002 and p = 0.006, respectively), but also neutrophil random migration of septic preterm and term infants were significantly lower than that of adults (p = 0.001 and p = 0.005, respectively). There was no relationship between the nature of causative microorganism and neutrophil random migration or chemotactic activity. Polymorphonuclear leukocytes chemotaxis was significantly lower in preterm with sepsis compared with healthy preterm-term infants and adults. These findings may indicate deterioration in neutrophil functions in premature babies under stress but more detailed studies with larger groups are needed.     

An investigation of the anger levels of residents: medical compared with surgical disciplines

Objective: To evaluate medical and surgical residents'' anger levels with regard to the department in which they worked, seniority, sex, satisfaction with their work environment, and the number of nightshifts worked per month. The specific situations and persons at whom residents reacted with anger were also investigated. Methods: 116 randomly selected residents staffed in a university hospital (62 medical and 54 surgical residents) were enrolled. The trait anger and anger expression scale was used to find out the personal anger levels of each participant. The participants also clarified the persons and situations that made them angry at work. Results: Trait anger levels were greater in the surgical residents in their first two years when compared with levels of their senior colleagues (p = 0.033). Mean trait anger levels were greater in the residents who were not satisfied with their department (p = 0.004). Anger levels were not found to be related to the number of shifts per month. Male residents had higher levels of anger than female colleagues (p = 0.019). Conclusion: Residents in clinical sciences seem to have the potential to benefit from a screening process in terms of anger and its subcomponents by means of a tool such as the trait anger and anger expression scale during their residency.     

A six-year study on Vibrio cholerae in southeastern Iran

Cholera continues to be an important public health problem among many poorer communities. In order to determine the epidemiology of Vibrio cholerae in southeastern Iran, 3,594 patients with watery diarrhea, who were referred to the hospitals from Zabol city and 45 neighboring rural populations of Sistan-Blouchestan province, were investigated over a period of 6 years (1997 - 2002). V. cholerae strains were isolated from 362 samples (10.07%). Isolation of V. cholerae in this sample decreased from 22.47% in 1997 to 0% in 2002. Individuals of all ages and social and economic strata were affected. Among the patients with cholera in the present study, only 24 (6.6%) lived in an urban area; 270 (74.6%) of the patients had been referred from rural areas, and the remaining 68 (18.8%) were from neighboring Afghanistan. V. cholerae O1 Ogawa and NAG vibrios were found in 92.8 and 7.2% of patients, respectively. Among the 362 samples, 244 were collected from inpatients and 118 were from outpatients. Twelve of these patients died because of the severity of their disease, severe dehydration and electrolytes imbalance. The priorities for cholera control remain public health interventions through improved water and sanitation, improved surveillance and access to health care facilities, and further development of appropriate vaccines.     

A newborn infant with generalized glutathione synthetase deficiency

Pyroglutamic aciduria (5-oxoprolinuria) is a rare autosomal recessive disorder caused by either glutathione synthetase deficiency (GSSD) or 5-oxoprolinase deficiency. The severe form of the disease, generalized GSSD, is characterized by acute metabolic acidosis, usually present in the neonatal period with hemolytic anemia and progressive encephalopathy. We report a female infant who had a severe metabolic acidosis with high anion gap, hemolytic anemia, and hyperbilirubinemia. High level of 5-oxoproline was detected in her urine and a diagnosis of generalized GSSD was made. She died of severe metabolic acidosis and sepsis at the age of six weeks.     

Serum insulin-like growth factor 1 and growth hormone levels of hypoxic-ischemic newborns

A number of growth factors, their binding proteins, and their receptors have been shown to be induced in the hypoxic-ischemic (HI) brain. In this prospective study, we aimed at determining the levels of insulin-like growth factor 1 (IGF-1), growth hormone (GH), and cortisol in HI babies and at identifying whether they differ from the levels of control infants. The serum IGF-1 levels were measured after the first 12-24 h of life, and the measurements were repeated on the 5th and 10th days of life for babies with HI encephalopathy (n = 18) and on the 10th day of life for controls (n = 19). Blood samples for measurement of cortisol and GH from both HI and control groups were collected after the first 12-24 h of life. There were 11 babies in the mild-to-moderate (stages I and II) group and 7 babies in the severe (stage III) group according to Sarnat and Sarnat. The IGF-1 levels of the HI group measured after 12-24 h [78.5 +/- 27.9 (range 9-123.4) ng/ml] and on the 10th day [72.2 +/- 36.8 (range 29.7-159.2) ng/ml] of life were statistically significantly lower than the IGF-1 levels of the control group [121.5 +/- 50.4 (range 74.4-280.5) ng/ml and 133.1 +/- 34.4 (range 65.9-202) ng/ml, respectively] (p = 0.002 and p = 0.001, respectively). But there was no statistically significant difference between mild-to-moderate HI group and severe HI group in terms of IGF-1 levels after 12-24 h and 5 and 10 days of life (p > 0.05). Also there was no statistically significant difference in IGF-1 values after the first 12-24 h and after 10 days of life between HI subjects who died or survived (p > 0.05). The GH levels of the HI group after the first 12-24 h of life [34.6 +/- 32.3 (range 0.1-120) mIU/l] were statistically significantly higher than those in the control group [10.4 +/- 4.5 (range 3.7-16.9) mIU/l] (p = 0.005). There was no statistically significant difference in the serum cortisol levels between HI and control groups after the first 12-24 h of life [18.7 +/- 17.0 (range 1.6-65.1) microg/dl vs. 10.8 +/- 5.4 (range 3.0-23.2) microg/dl] (p > 0.05). No statistically significant correlation was found between IGF-1 levels and GH and cortisol levels of the HI encephalopathy group [r = -0.113 (p > 0.05) and r = 0.108 (p > 0.05), respectively]. In conclusion, this study showed decreased levels of serum IGF-1 and increased levels of GH which may be secondary to serum IGF-1 influx from the circulation to the brain as a protective mechanism or may be due to some cytokines which alter the GH/IGF axis, inhibit the action of IGF-1, and stimulate IGF-binding protein 1.     

Brain metastasis from esophageal carcinoma

Brain metastasis from esophageal carcinoma is rare. In our center, among 301 cases of esophageal cancer referred for radiotherapy during a 14-year period, brain metastasis from esophageal carcinoma was detected in one case. An unusual case of esophageal carcinoma that presented with brain metastasis is reported.     

Prevalence and pattern of antimicrobial resistance of Shigella species among patients with acute diarrhoea in Karaj,Tehran, Iran

The study was carried out to determine the prevalence and pattern of antimicrobial resistance of Shigella species among patients with acute diarrhoea in Karaj, Tehran, Iran. The study included all acute diarrhoea patients who visited the hospitals and treatment centres of Karaj during November 2001-October 2002. Of 734 stool samples collected from patients with acute diarrhoea and analyzed for Shigella spp., 123 (16.8%) yielded Shigella spp. (7.5% Shigella flexneri, 5.2% S. sonnei, 2.6% S. dysenteriae, and 1.5% S. boydii). Of the Shigella isolates, 90.8% were resistant to one or more antimicrobial agent(s), and 87.8% were multidrug resistant. The most common resistance was to tetracycline (73.5%), trimethoprim-sulphamethoxazole (70.4%), and amoxicillin-clavulanic acid (50.0%). Resistance to cefixime, ciprofloxacin, ceftriaxone, and nalidixic acid was observed in 6.1%, 3.1%, 2.0%, and 1.0% of the isolates respectively. These findings suggest that Shigella spp. may be an important aetiological agent of diarrhoea with a high rate of drug resistance in this region, which requires further study.     

Pentoxifyllin Attenuates the Systemic Inflammatory Response Induced During Isolated Limb Perfusion With Recombinant Human Tumor Necrosis Factor-α and Melphalan

Background: Isolated limb perfusion (ILP) with recombinant human tumor necrosis factor- (rhTNF-) and melphalan harbors the risk of septic shock–like syndrome. Pentoxifyllin (PTX) produced a beneficial effect on cytokine response and survival in animal experiments of septic shock, and we were interested to explore its effect during TNF-ILP in humans.Methods: Eighteen consecutive patients underwent TNF-ILP and received PTX (30 mg/kg/day), whereas another 13 consecutive patients did not. PTX was given systemically after the limb extracorporeal circulation was started. Cardiac index, systemic vascular resistance (SVR), and pulmonary vascular resistance were recorded via a Swan-Ganz catheter. Blood levels of TNF-, interleukin-6, procalcitonin, and lipopolysaccharide-binding protein were determined before, during, and after ILP.Results: After reperfusion, systemic levels of TNF- were significantly less increased in the PTX group (peak, 2.8 vs. 1.3 ng/mL; P < .05), as were interleukin-6 values (peak, 68 vs. 22 pg/mL; P < .02) and lipopolysaccharide-binding protein plasma levels (peak, 215 vs. 105 g/mL; P < .03). Differences in cardiac index, SVR, and mean arterial blood pressure were not significantly different. Norepinephrine or dobutamine to maintain SVR was less required in the PTX group.Conclusions: PTX attenuates systemic cytokine production and influences components of the systemic inflammatory response after TNF-ILP. PTX may play a beneficial role in the management of septic shock–like syndrome, particularly in patients with leakage from the ILP circuit.Presented at the 55th Annual Meeting of the Society of Surgical Oncology, Denver, Colorado, March 14–17, 2002.     

Intrathecal administration of PNA targeting galanin receptor reduces galanin-mediated inhibitory effect in the rat spinal cord

Peptide nucleic acids (PNA) are nucleic acid analogues containing neutral amide backbone, forming stable and tight complexes with complementary DNA/RNA. However, it is unclear whether unmodified PNA can efficiently penetrate neuronal tissue in order to act as antisense reagent. Here we show that intrathecal (i.t.) injection of an unmodified antisense PNA complementary to the rat galanin receptor type 1 (GalR1) mRNA is able to block the inhibitory effect of i.t. administered galanin on spinal nociceptive transmission. Autoradiographic ligand binding studies using [125I]galanin show that the unmodified PNA is able to reduce the density of galanin binding sites in the dorsal horn. Thus, unmodified PNA applied i.t. appears to function as an effective antisense reagent in rat spinal cord in vivo.