Adaptation mechanisms to the short intestine. Influence of the biliopancreatic factor: experimental study

Massive small bowel resection that results in short bowel syndrome brings about regulatory mechanisms in the remaining intestine aimed at preventing the ensuing malabsorption. The purpose of the present study was to determine the role of pancreatic and biliary secretions in intestinal adaptation after small bowel resection. To do so, both pancreatic and biliary fluids were prevented from reaching the lumen of most of the small bowel. Four groups of animals were prepared: I) control group; II) eighty percent small bowel resection; III) duodenoileal by-pass; and IV) duodenoileal by-pass plus small bowel resection. After a fifteen days recovery period, the following were recorded: animal weight; plasma protein, BUN, cholesterol, glucose, and Ca++; the length and diameter of the jejunum and ileum, the height of the mucosal layer, and microvilli density. Intestinal adaptation was excellent in animals after small bowel resection. All animals in group IV died due to severe malabsorption. Diversion of pancreatic and biliary juice in animals with duodenoileal by-pass did not prevent intestinal adaptation. We conclude that the effect of pancreatic and biliary juice on intestinal adaptation is additive to that of other putative hormonal mechanisms.     

Characterization of high-altitude pulmonary hypertension in the Kyrgyz: association with angiotensin-converting enzyme genotype

Previous studies have suggested a genetic component in susceptibility to hypoxia-induced pulmonary hypertension. We therefore estimated the prevalence of high-altitude pulmonary hypertension (HAPH) in a Kyrgyz population and whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene associates with HAPH. An electrocardiographic survey of 741 highlanders demonstrated electrocardiogram signs of cor pulmonale in 14% of subjects. Pulmonary artery hemodynamics measured in an independent group of 136 male highlanders with symptoms of dyspnea at altitude revealed established pulmonary hypertension (mean pulmonary artery pressure [MPAP] > or = 25 mm Hg) in 20%. However, 26% of the normal subjects demonstrated an exaggerated response (twofold or greater increase in MPAP) to inhalation of 11% oxygen, and were classified as hyperresponsive. Ten-year follow-up of this group revealed increases in the MPAP, but not in normal subjects. Comparison of ACE I/D genotypes in the catheterized group revealed a threefold higher frequency of the I/I genotype in highlanders with HAPH, compared with normal highlanders (chi2 = 11.59, p = 0.003). In addition, MPAP was higher in highlanders with the I/I genotype (26.9 +/- 4.0 mm Hg) compared with the I/D genotype (20.6 +/- 1.2 mm Hg) or the D/D genotype (18.3 +/- 0.9 mm Hg) (p < 0.05). We conclude that HAPH is associated with ACE I/D genotype among Kyrgyz highlanders and the development of HAPH in this population and may be predicted by hyperresponsiveness to acute hypoxia.     

Penitentiary population of Mycobacterium tuberculosis in Kyrgyzstan: Exceptionally high prevalence of the Beijing genotype and its Russia-specific subtype

Here, we present results of the first study of the Mycobacterium tuberculosis genotypes circulating in Kyrgyzstan. We focused on the incarcerated population known to be at high-risk for tuberculosis (TB) and with a significant impact on TB incidence in the general population. Beijing genotype was detected in 42 of 56 M. tuberculosis sputum-extracted DNA samples from newly-diagnosed adult pulmonary TB patients. RIF and INH resistance was genotypically detected in 28% and 55% samples; 13 of 15 MDR strains belonged to Beijing genotype. 12-locus MIRU-VNTR typing showed 8 of 56 samples to be mixed cases; 7 of them contained a Beijing strain. MIRU analysis demonstrated a high homogeneity of the studied collection (HGI = 0.66) while 28 of 56 strains had a profile 223325153533 corresponding to Beijing/M2 subtype highly prevalent in different Russian settings. Three hypervariable loci, QUB-3232, VNTR-3820 and VNTR-4120, permitted to further subdivide 28 Beijing/M2 strains into 11 subtypes shared by 1 to 9 strains. To conclude, all markers taken together, the penitentiary population of M. tuberculosis in Kyrgyzstan exhibited a strong genetic affinity to Russia and a weak relatedness to East Asia.     

Interleukin-1 regulates proliferation and differentiation of oligodendrocyte progenitor cells

Interleukin-1 (IL-1) is a pleiotropic cytokine expressed during normal CNS development and in inflammatory demyelinating diseases, but remarkably little is known about its effect on oligodendroglial cells. In this study we explored the role of IL-1beta in oligodendrocyte progenitors and differentiated oligodendrocytes. The effects of IL-1beta were compared to those of IL-1 receptor antagonist, the specific inhibitor of IL-1 activity, since progenitors and differentiated oligodendrocytes produce IL-1beta and express IL-1 receptors. Unlike other proinflammatory cytokines (TNFalpha and IFNgamma), IL-1beta was not toxic for oligodendrocyte lineage cells. However, this cytokine inhibited proliferation of oligodendrocyte progenitors in the presence of growth factors (PDGF plus bFGF). This was evidenced by a significant decrease in both cells incorporating bromodeoxyuridine (45%) and total cell numbers (57%) after 6 days of treatment. Interestingly, IL-1beta blocked proliferation at the late progenitor/prooligodendrocyte (O4+) stage but did not affect proliferation of early progenitors (A2B5+). Inhibition of proliferation paralleled with promotion of differentiation, as revealed by the increased percentage of R-mab+ cells (6.7-fold). Moreover, when oligodendrocyte progenitors were allowed to differentiate in the absence of growth factors, treatment with IL-1beta promoted maturation to the MBP+ stage (4.2-fold) and survival of differentiating oligodendrocytes (2.1-fold). Regarding intracellular signaling, IL-1beta activated the p38 mitogen-activated protein kinase (MAPK) but not the p42/p44 MAPK and, when combined with growth factors, intensified p38 activation but inhibited the growth-factor-induced p42/p44 activation. IL-1beta also induced a time-dependent inhibition of PFGF-Ralpha gene expression. These results support a role for IL-1beta in promoting mitotic arrest and differentiation of oligodendrocyte progenitors as well as maturation and survival of differentiating oligodendrocytes.     

Epidemiological assessment of levodopa use in Spain, 1990-1995. Persistent, low consumption in the south

Parkinson's disease (PD) is considerably underdiagnosed in Spain and its treatment relies mainly on levodopa (LD), a drug enjoying good access country-wide. In order to identify regions with the highest potential for improvement in the quality of life of PD patients, we evaluated total sales of levodopa in Spanish provinces during the period 1990-1995, using a reported method. Total annual crude sales in the country were medium-low and increased with time. When adjusted for age and infant mortality rates (IMRs), taken as an index of socio-sanitary development, annual LD sales become stable and similar to those in the reference population, Sweden 1994. Provincial LD use (LDU) showed a wide variation in annual levels and time trends, with a north-south gradient in evidence. Statistically significant clustering was seen, with the lowest crude age-adjusted and age- and IMR-adjusted LD sales in the south-west and moderately high levels in north-central and north-west provinces. The results show that LDU in Spain is medium-low, and that demographic and social factors may underlie geographical differences in LD sales. The remarkably low LDU in selected provinces in the south-west of the country might reflect deficient PD detection and/or treatment amenable to control.