Pathology of the kidney and liver in the experimental leptospirosis of the guinea-pig

Summary A light and electron microscopy study of the experimental leptospirosis of the guinea pig wasdone. The earliest lesion found was located at the cell membrane, with partial or total disappearance of the brush border of the cells of the proximal tubuli as well as partial disappearance and distortion of the microvilli of the hepatic cells. Intercellular spaces were found to be enlarged both in the liver and kidney. Capillaries showed endothelial cell tumefaction and, sometimes, disjunction of the endothelial lining, a finding also in accordance with the basic pathology of the disease. Only at the late phase of the disease, mainly at the agonic period, that pathology of the organelles such mitochondria was found. However, a definite increase of dense bodies whose origin was discussed, was found since the early phase of the disease. Also described, a mild but definite focal glomerular lesion, which provides anatomical basis for the proteinuria seen in the disease. The above described basic pathology of the disease is in accordance with the possibility of a toxin as the main mechanism acting for leptospiral pathogenicity.

---

Die Pathologie der Mere und der Leber bei der experimentellen Leptospirose des MeerschweinchensLicht- und elektronenmikroskopische Untersuchungen

Zusammenfassung Die erste Veränderung wurde an der Zellmembran beobachtet, zusammen mit teilweiser oder vollständiger Zerstörung des Bürstensaumes der proximalen Nierenkanälchen sowie der Mikrovilli der Leberzellen. Die intercellulären Räume der Leber und Niere waren erweitert. An den Blutcapillaren fanden sich endotheliale Schwellungen und manchmal auch Loslösung des Endothels. Eine pathologische Veränderung der Mitochondrien wurde nur während der Endphase der Krankheit gesehen, doch waren dense bodies schon von Anfang an vorhanden. Außerdem wurde auch eine leichte glomeruläre Läsion gefunden, welche die anatomische Grundlage der Proteinurie darstellen mag. Diese Befunde lassen die Annahme einer toxischen Wirkung als Grundlage der Pathogenese der Leptospirose zu.

---

---

This work was aided by grantnumber DA-ARO-49-092-65-G61 of the U.S. Army Research Office and by the Fundação de Amparo à Pesquisa de S. Paulo.     

Post–conditioning reduces infarct size in the isolated rat heart: Role of coronary flow and pressure and the nitric oxide/cGMP pathway

We aimed to assess the role of the nitric oxide (NO)–cGMP pathway in cardioprotection by brief intermittent ischemias at the onset of reperfusion (i.e., post–conditioning (Post–con)). We also evaluated the role of coronary flow and pressure in Post–con. Rat isolated hearts perfused at constant– flow or –pressure underwent 30 min global ischemia and 120 min reperfusion. Post–con obtained with brief ischemias of different duration (modified, MPost–con) was compared with Post–con obtained with ischemias of identical duration (classical, C–Post–con) and with ischemic preconditioning (IP). Infarct size was evaluated using nitro–blue tetrazolium staining and lactate dehydrogenase (LDH) release. In the groups, NO synthase (NOS) or guanylyl–cyclase (GC) was inhibited with LNAME and ODQ, respectively. In the subgroups, the enzyme immunoassay technique was used to quantify cGMP release. In the constant–flow model, M–Post–con and C–Post–con were equally effective, but more effective than IP in reducing infarct size. The cardioprotection by M–Post–con was only blunted by the NOS–inhibitor, but was abolished by the GC–antagonist. Post–ischemic cGMP release was enhanced by MPost–con. In the constant–pressure model IP, M–Post–con and C–Post–con were equally effective in reducing infarct size. Post–con protocols were more effective in the constant–flow than in the constant–pressure model. In all groups, LDH release during reperfusion was proportional to infarct size. In conclusion, Post–con depends upon GC activation, which can be achieved by NOS–dependent and NOS–independent pathways. The benefits of M– and CPost–con are similar. However, protection by Post–con is greater in the constant–flow than in the constant–pressure model.     

How to manage splenic rupture during major liver resection?

Spontaneous splenic rupture is a rare but life threatening complication of major liver resection with only five reported cases during major liver resection under hepatic vascular occlusion. We report two cases of splenic rupture during liver resection including the first case during portal triad clamping. In both patients, the hemorrhage was stopped by removing the vascular clamp. A splenectomy was performed in both patients and liver resection was completed under vascular clamping without complications. Although very rare, physicians should be aware of the possibility of splenic rupture during liver resection because instead of increasing vascular occlusion, clamp removal usually stops the hemorrhage.     

The turbinate flap for oronasal fistula closure

Extensive scarring may limit available local tissue for closure of the nasal epithelial lining in oronasal fistulae, as frequently seen in cleft patients. A pedicled mucoperiosteal flap harvested from the inferior turbinate can be a valuable alternative to close such defects. Due to dense vascularity of the conchal mucosa, an inferior turbinate flap with an average size of 9.9 cm may be harvested. This is illustrated in a case of a large nasovestibular fistula in a patient after premaxillary osteoplasty and anatomic studies.     

Seminal plasma cytokines and chemokines in prostate inflammation: interleukin 8 as a predictive biomarker in chronic prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia

OBJECTIVE: This prospective study quantified cytokine and chemokine levels in seminal plasma of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH), to evaluate inflammatory mediators as possible surrogate markers for diagnosis and treatment efficacy. METHODS: Seminal plasma levels of eight cytokines and nine chemokines were evaluated by multiplex arrays in 83 men: 20 healthy controls and 9 men with CP/CPPS IIIA, 31 with CP/CPPS IIIB, and 23 with BPH. Prostate samples obtained by transurethral resection of the prostate from 13 patients with BPH were analysed by immunohistochemistry to detect interleukin 8 (IL-8)-producing cells and characterise inflammatory infiltrates. RESULTS: Significantly increased levels of cytokines (IL-1alpha, IL-1beta, IL-6, IL-10, IL12p70) and chemokines (CCL1, CCL3, CCL4, CCL17, CCL22, CXCL8/IL-8) were observed in seminal plasmas from patients with CP/CPPS or BPH. However, only IL-8 was significantly elevated compared to controls (median [quartiles] 1984 [1164-2444] pg/ml), in patients with CP/CPPS IIIA (15,240 [10,630-19,501] pg/ml; p<0.0001), CP/CPPS IIIB (2983 [2033-5287] pg/ml; p=0.008), and BPH (5044 [3063-11,795] pg/ml, p<0.0001), discriminating CP/CPPS IIIA versus IIIB (accuracy=0.882+/-0.078; p=0.001). Inflammatory infiltrates were detected in prostate samples from 13 of 13 BPH patients, and IL-8-producing prostate cells in 11 of 13 samples. IL-8 concentration in seminal plasma was positively correlated with symptom score and prostate-specific antigen levels both in CP/CPPS and BPH patients. CONCLUSIONS: IL-8 is expressed in situ by epithelial and stromal prostate cells and is functional, as shown by recruitment of cells expressing cognate receptors in BPH prostate tissue, indicating its involvement in disease pathogenesis. Among all the cytokines and chemokines analysed, IL-8 appears to be the most reliable and predictive surrogate marker to diagnose prostate inflammatory conditions, such as CP/CPPS and BPH.     

Stabilization of endotracheal tube--a technical note

The vital need to retain closed-circuit airways during maxillofacial surgery has led to several innovations in anesthetic tube placement and stabilization. Several designs and alterations of endotracheal tubes have been described and are currently in use. These range from suturing the tubing to the patient's scalp to fabricating maxillofacial prostheses. In this report, an easy method for securing anesthetic tubes is described. This technique has been used successfully at our institution.     

Genome-wide RNAi screen of Ca(2+) influx identifies genes that regulate Ca(2+) release-activated Ca(2+) channel activity

Recent studies by our group and others demonstrated a required and conserved role of Stim in store-operated Ca(2+) influx and Ca(2+) release-activated Ca(2+) (CRAC) channel activity. By using an unbiased genome-wide RNA interference screen in Drosophila S2 cells, we now identify 75 hits that strongly inhibited Ca(2+) influx upon store emptying by thapsigargin. Among these hits are 11 predicted transmembrane proteins, including Stim, and one, olf186-F, that upon RNA interference-mediated knockdown exhibited a profound reduction of thapsigargin-evoked Ca(2+) entry and CRAC current, and upon overexpression a 3-fold augmentation of CRAC current. CRAC currents were further increased to 8-fold higher than control and developed more rapidly when olf186-F was cotransfected with Stim. olf186-F is a member of a highly conserved family of four-transmembrane spanning proteins with homologs from Caenorhabditis elegans to human. The endoplasmic reticulum (ER) Ca(2+) pump sarco-/ER calcium ATPase (SERCA) and the single transmembrane-soluble N-ethylmaleimide-sensitive (NSF) attachment receptor (SNARE) protein Syntaxin5 also were required for CRAC channel activity, consistent with a signaling pathway in which Stim senses Ca(2+) depletion within the ER, translocates to the plasma membrane, and interacts with olf186-F to trigger CRAC channel activity.     

Helicobacter pylori virulence factors as tools to study human migrations

Helicobacter pylori is one of the most common infections worldwide. In most individuals it consists in a lifelong host-pathogen relationship without consequences, but in some subjects it is associated with peptic ulcer disease and gastric cancer. Polymorphism in genes that code bacterial virulence factors, cagA and vacA, are independently associated with the infection severe outcomes and are geographically diverse. In the last decade, accumulated knowledge allowed to characterize typical H. pylori strain patterns for all the major human populations; patterns that can be used to study the origin of specific human groups. Thus, the presence or absence of cagA, cagA EPIYA genotypes, and vacA subtypes can be used as tools to study not only the geographic origin of specific human populations, but also to identify markers of historical contact between different ethnicities. We report here a study including a set of native Amazon Amerindians that had supposedly been some, but little, contact with European Brazilian colonizer and/or African slaves. They harbor H. pylori strains in a mixed pattern with Asian and Iberian Peninsula characteristics. It is possible that this finding represents H. pylori recombination upon short contact between human groups. Alternatively, it could be due to a founder effect from a small cluster of Asian origin native Americans.