Adenosine relaxation in small retinal arterioles requires functional Na-K pumps and K(ATP) channels

PURPOSE: To study the effect of Na-K pump and K(ATP) channel inhibition on the diameter and the adenosine-induced vasodilation of small retinal arterioles. METHODS: Thirty isolated porcine arterioles with a diameter of approximately 70 microm were mounted in a double-barrelled pipette system placed in an organ bath, and diameter changes were studied under isobaric no-flow conditions. After an equilibration period, the arterioles were incubated with the Na-K pump inhibitors ouabain and low K(+) medium or the K(ATP) channel inhibitor glibenclamide, and spontaneous diameter changes were studied. Subsequently, the arterioles were precontracted and the adenosine concentration response curve was measured with and without the presence of inhibitors. RESULTS: Inhibition of the Na-K pump elicited a significant decrease in the spontaneous diameter of the vessels (P = 0.047), whereas no change in the spontaneous diameter was induced by inhibition of the K(ATP) channels (P = 0.754). Inhibition of the Na-K pump with ouabain or with low K(+) medium, as well as inhibition of the K(ATP) channels with glibenclamide, both diminished the adenosine induced vasodilation (P = 0.003, P = 0.01, and P = 0.003, respectively). CONCLUSION: The adenosine-induced vasodilation of small retinal arterioles involves the K(ATP) channels and the Na-K pump. Changes in the metabolism of adenosine as well as the activity of the K(ATP) channels or the Na-K pump can be expected to influence the retinal blood flow.     

Bradykinin relaxation in small porcine retinal arterioles

PURPOSE: To study changes in the spontaneous diameter of small retinal arterioles and bradykinin (BK)-induced vasodilation during inhibition of the synthesis of nitric oxide (NO), prostaglandins (PGs), and cytochrome P450 2C8/9-dependent endothelial-derived hyperpolarizing factor (EDHF). METHODS: Forty-eight isolated porcine arterioles with a diameter of approximately 70 microm were mounted in a double-barreled pipette system placed in an organ bath, and diameter changes were studied under isobaric conditions. After an equilibration period, the arterioles were incubated with inhibitors of the synthesis of NO, PGs, or cytochrome P450 2C8/9-dependent EDHF, and spontaneous diameter changes were studied. Subsequently, the arterioles were precontracted, and the diameter was assessed after addition of BK in cumulative concentrations. RESULTS: Inhibition of NOS elicited a significant decrease in the spontaneous diameter of the vessels (P = 0.028), whereas no change in the spontaneous diameter was induced by inhibition of PG or cytochrome P450 2C8/9 dependent EDHF synthesis (P = 0.35 and P = 0.75, respectively). The vasodilating effect of BK was decreased by inhibition of NO (P = 0.002) but not by inhibition of prostaglandin or cytochrome P450 2C8/9-dependent EDHF synthesis (P = 0.82 and P = 0.94, respectively). CONCLUSIONS: The results suggest the presence of a spontaneous release of NO, which keeps the retinal microcirculation dilated under normal conditions. The finding of BK-induced relaxation being dependent on the NO synthase (NOS), but not on PGs or cytochrome P450 2C8/9-dependent EDHF may be of importance for understanding the microcirculatory effects of pharmacologic compounds affecting the BK metabolism, such as angiotensin-converting enzyme (ACE) inhibitors.     

Renal ischemia-reperfusion injury in the rat is prevented by a novel immune modulation therapy

BACKGROUND: Vasogen Inc.'s (Mississauga, Ontario, Canada) immune modulation therapy (IMT) is a therapy in which cells from the patient's own blood are modified by ex vivo exposure to specific physicochemical stressors, including oxidation, ultraviolet (UV) light, and an elevated temperature. The therapy has been shown to have a beneficial effect in models of inflammation and vascular diseases. This study tested the hypothesis that IMT can prevent renal ischemia-reperfusion (I/R) injury in rats. METHODS: Whole blood was collected from syngeneic age-matched donors by cardiac puncture. It was treated with a combination of controlled physiochemical stressors consisting of elevated temperature, a gas mixture of medical oxygen containing ozone, and UV light. The treated blood (150 microL) was injected in the gluteal muscle. Control animals received the same volume of untreated blood or physiological saline. Transient (45 or 60 minutes) left-renal ischemia was produced with simultaneous contralateral nephrectomy in treated and control spontaneously hypertensive rats (SHR). Young and old male and female rats were studied. Plasma creatinine, diuresis, and the survival rates of each group were compared. Renal apoptosis-necrosis was estimated by DNA laddering, histology, and in situ terminal deoxynucleotidyl transferase assay. mRNA levels of several regulators of apoptosis-regeneration were determined in control and postischemic kidneys by Northern blotting. RESULTS: IMT pretreatment of SHR significantly reduced renal I/R injury compared with equivalent placebo treatments consisting of untreated blood- or saline-injected SHR, as evidenced by a significant increase of the survival rate curves in young and old male SHR, which correlated with 24-hour postischemic diuresis. The increases in plasma creatinine following renal I/R were significantly lower in IMT-treated young male and old female SHR compared with saline or untreated blood-injected controls. Dilution analysis showed that the protective effect of treated blood was lost by dilution. Loss of epithelial cells was reduced in IMT-treated rats, with a significant decline in the peak of apoptosis 12 hours after acute ischemic renal injury. IMT did not modify the pattern of mRNA levels of several genes involved in the inflammation and regeneration processes. CONCLUSION: Our data demonstrate that IMT prevents the destruction of kidney tissue and the resulting animal death caused by renal I/R injury.     

Participants' perception of impact of a workshop on their preventive practices

A 90-minute interactive workshop, offered to small groups on request, was developed to help physicians include evidence-based preventive interventions in their practices. Between 25 September 1996 and 10 December 1997, 593 family physicians throughout the Province of Quebec (Canada) participated in one of the 40 workshops presented in all the regions of Quebec. Almost all participants (98%) completed the self-administered questionnaire. Their opinion of the achievement of three workshop objectives were evaluated using a seven-point Likert scale (-3 to +3)as their perception of the direct impact of the workshop on their practice. The workshop objectives were reached to a high degree: 2.1 (sd 0.90) for prescribing a proper check-up for adults; 1.83(sd 1.02) for explaining to the patient the reasons motivating his/her choice to include or exclude certain tests; 2.09 (sd 0.93)for using concrete and useful tool facilitating the integration of preventive measures in his/her professional practice. Female physicians and those under 40 perceived that the objectives were reached to a greater degree. Participants indicate their intention to modify their practice according to the clinical practice guidelines presented in the workshop.     

Relations between background,process and outcome in the first semester of a new,problem-based medical curriculum

The authors investigated the relations between students' background (gender, age, study experience), learning process (learning approach, independent study time) and outcome (examination results, satisfaction) in the first semester of a new, integrated undergraduate medical curriculum, combining PBL and conventional learning methods. Data were obtained from official records and from a questionnaire answered by 113 students (response rate 92%). Variables were subjected to multivariate analyses. Significantly more males than females reported a strategic learning approach, and these students were less satisfied and more prone to fail on the exam. Time used on independent study did not predict examination results. The authors suggest that in a problem-based curriculum, the strategic males should be identified and supervised to improve the qualitative aspects of their study behaviour.     

Novel polymorphisms in the somatostatin receptor 5 (SSTR5) gene associated with bipolar affective disorder

The somatostatin receptor 5 (SSTR5) gene is a candidate gene for bipolar affective disorder (BPAD) as well as for other neuropsychiatric disorders. The gene is positioned on chromosome 16p13.3, a region that has been implicated by a few linkage studies to potentially harbor a disease susceptibility gene for BPAD. Recent evidence shows that the dopamine D2 receptor (DRD2) and SSTR5 interact physically to form heterodimers with enhanced functional activity. Brain D2 dopamine receptors are one of the major targets of neuroleptic treatments in psychiatric disorders. In this study we systematically screened the promoter and coding region of the SSTR5 gene for genetic variation that could contribute to the development of neuropsychiatric disorders. Eleven novel single nucleotide polymorphisms (SNPs) were identified including four missense SNPs, Leu48Met, Ala52Val, Pro109Ser and Pro335Leu. We carried out an association study of BPAD using 80 Danish cases and 144 control subjects, and replication analysis using 55 British cases and 88 control subjects. For the Danish population, association was suggested between silent SNP G573A and BPAD (P = 0.008). For the British population we found association to BPAD with missense mutation Leu48Met (P = 0.003) and missense mutation Pro335Leu (P = 0.004). The statistical significance of the association was, however, greatly reduced after correcting for multiple testing. When combining genotypes from Leu48Met and Pro335Leu into haplotypes, association to BPAD was found in the British population (P = 0.0007). This haplotype association was not replicated in the Danish population. Our results may indicate that the SSTR5 gene is involved in the etiology of BPAD or may exist in linkage disequilibrium with a susceptibility gene close to SSTR5. However, given the marginal statistical significance and the potential for false-positive results in association studies with candidate genes, further studies are needed to clarify this hypothesis.     

Prevalence of gonococcal and chlamydial infections and sexual risk behavior among youth in Addis Ababa,Ethiopia

BACKGROUND: No community-based study on the magnitude of sexually transmitted diseases (STDs) has ever been conducted among young people in Ethiopia. GOAL: To assess the magnitude of Chlamydia trachomatis and Neisseria gonorrhoeae infections and status of sexual risk behavior among youths (15-24 years old) in Addis Ababa, Ethiopia. STUDY DESIGN: Youths in or out of school residing in two (of the six) administrative zones in Addis Ababa served as the study population. Participants filled out a self-administered questionnaire related to sexuality and its sociocultural determinants. First-void urine (FVU) was analyzed for gonorrhea and chlamydial infection by polymerase chain reaction (PCR). RESULTS: A total of 561 youths took part in the study. Urine PCR was performed for 522 of them. Nine subjects (1.7%) were found to have and N gonorrhoeae and C trachomatis infections. There were five cases (1.0%) involving each agent. Double infection was noted in one female subject. All but one of the infections were detected among the out-of-school youths (chi-square = 4.5; < 0.05). None of these subjects complained of symptoms suggestive of an active STD. One-third (188/561) reported having had sexual intercourse. The prevalence among sexually active youths was thus 4.8% (9/188) for both infections combined (2.7% for each agent). While 7/52 (13.5%) of the sexually active females were found to also have STDs, only 2/136 (1.5%) of the males had an STD (chi-square = 8.0; < 0.01). Report of sexual activity was significantly associated with being male, an age of >/=20 years, out-of-school status, and report of alcohol/khat (amphetamine-like substance) consumption. Females reported less condom use, whether they were in or out of school and independent of age. CONCLUSIONS: Out-of-school youths, especially females, took more sexual risk and were exceedingly susceptible to STDs. This calls for alternative group-targeted strategies for sex education, disease prevention, and STD screening and management.     

Early psychomotor slowing predicts the development of HIV dementia and autopsy-verified HIV encephalitis

OBJECTIVES- To ask if slowed motor speed predicts later human immunodeficiency virus (HIV) dementia and HIV encephalitis. METHODS- In 100 deceased acquired immunodeficiency syndrome (AIDS) patients prior results from repeated testing of the movement reaction time test were correlated with later clinical signs of HIV dementia and with neuropathological signs of HIV encephalitis. Autopsy was performed in 72 patients. RESULTS- Movement reaction time 1-2 years prior to death, or at the time of clinical AIDS diagnosis predicted both development of HIV dementia (P<0.05) and HIV encephalitis at autopsy (P<0.01). CONCLUSION- Testing for early psychomotor slowing may be used to identify patients at risk of HIV dementia and HIV encephalitis.