Microproteínas urinarias marcadoras de daño renal en pacientes con glomerulopatías / Urinary microprotein markers of renal disease in patients with glomerulopathies / Microproteínas urinárias marcadoras de lesão renal em pacientes com glomerulopatias

En las glomerulopatías, las Microproteínas Urinarias (MU) se eliminan por distintos mecanismos fisiopatológicos. El objetivo del trabajo fue correlacionar las MU con el daño histológico evaluado en la punción biopsia renal (PBR) de pacientes con diversas glomerulopatías. Se estudiaron 44 orinas espontáneas (33 mujeres y 11 varones) entre 18 y 71 años de edad, por el método de electroforesis bidimensional de uso clínico (2D UC). Las proteínas identificadas se dividieron en 5 grupos y se compararon con lesiones vasculares, glomerulares y túbulointersticiales; estas dos últimas se dividieron en crónicas y agudas. Las del grupo identificado como las "Tres Marías" (fragmento de 35 kDa de la proteína inhibidor de tripsina cadena pesada H4, Prostaglandina H2 sintasa y fragmento de 23 kDa del Perlecan) resultaron no ser marcadoras de daño tubular, sino de alteraciones glomerulares crónicas. La presencia de las mismas, con proteinuria, se observa antes de la caída de la filtración glomerular (<60 mL/min) y correlaciona con el 30% de glomérulos totalmente esclerosados (p<0,001). El grupo Triángulo, en la glomerulopatía, contiene a la Alfa-1 microglobulina (A1m) y a las cadenas livianas libres de Inmunoglobulinas (CLL), e indica lesión glomerular activa. Por lo tanto, las MU en glomerulopatías, responden a lesiones glomerulares activas y crónicas. Los perfiles proteicos urinarios hallados por la 2D UC permitieron conocer el grado de lesión en los distintos compartimentos renales.

In Glomerulopathies, urinary microproteins (UM) are eliminated by different pathophysiological mechanisms. The objective of this work was to correlate the UM with the histological damage evaluated in the renal biopsy through puncture of patients with various glomerular diseases. Forty-four urine samples (33 females, 11 males) aged 18 to 71 years old were studied by the method of two-dimensional electrophoresis of clinical use (2D UC). The identified proteins were divided into 5 groups and were compared with vascular injury, glomerular and tubulointerstitial injury, the latter in chronic and acute cases. The group identified as the "Three Marias" (fragment 35 kDa protein trypsin inhibitor heavy chain H4, prostaglandin H2 synthase and 23 kDa fragment of Perlecan), was not found as marker of tubular damage, but it was found in chronic glomerular disorders. The presence of this same group -with proteinuria- is seen before the collapse of the glomerular filtration rate (<60 mL/min) and it is correlated with 30% of fully sclerotic glomeruli (p<0.001). In glomerulopathy, the Triangle group: Alpha-1 microglobulin (A1m) and free Immunoglobulin light chains (FLC), indicates active glomerular injury. Therefore, the UM in glomerular diseases, respond to active and chronic glomerular lesions. Urinary protein profiles found by the 2D UC made it possible to know the degree of renal injury in different renal compartments.

Nas glomerulopatias, as Micro proteínas Urinárias (MU) são eliminadas através de diferentes mecanismos fisiológicos. O objetivo do trabalho foi relacionar as MU com o dano histológico avaliado na punção biópsia renal (PBR) de pacientes com diversas glomerulopatias. Foram estudadas 44 urinas espontâneas (33 mulheres e 11 homens entre 18 e 71 anos de idade), pelo método de eletroforese bidimensional de uso clínico (2D UC). As proteínas identificadas foram divididas em 5 grupos e comparadas com lesões vasculares, glomerulares e túbulo-intersticiais, estas duas últimas classificadas em crônicas e agudas. O grupo identificado como as "Três Marias" (fragmento de 35 kDa da proteína inibidora de tripsina cadeia pesada H4, Prostaglandina H2 sintase e fragmento de 23 kDa do Perlecam), resultaram não ser marcadoras de dano tubular, mas de alterações glomerulares crônicas. A presença de tais proteínas, com proteinúria, observa-se antes da queda da filtragem glomerular (<60 mL/min) e correlaciona com 30% de glomérulos totalmente esclerosados (p<0,001). O grupo Triângulo, na glomerulopatia, que contém a Alfa-1 microglobulina (A1m) e as cadeias leves livres de Imunoglobulinas (CLL) indicam lesão glomerular ativa. Portanto, as MU em glomerulopatias respondem a lesões glomerulares ativas e crônicas. Os perfis proteicos urinários encontrados pela 2D UC permitiram conhecer o grau de lesão nos diferentes compartimentos renais.

Development of an Ex Vivo Model for the Study of Cerebrovascular Function Utilizing Isolated Mouse Olfactory Artery

OBJECTIVE: Cerebral vessels, such as intracerebral perforating arterioles isolated from rat brain, have been widely used as an ex vivo model to study the cerebrovascular function associated with cerebrovascular disorders and the therapeutic effects of various pharmacological agents. These perforating arterioles, however, have demonstrated differences in the vascular architecture and reactivity compared with a larger leptomeningeal artery which has been commonly implicated in cerebrovascular disease. In this study, therefore, we developed the method for studying cerebrovascular function utilizing the olfactory artery isolated from the mouse brain. METHODS: The olfactory artery (OA) was isolated from the C57/BL6 wild-type mouse brain. After removing connective tissues, one side of the isolated vessel segment (approximately -500 microm in length) was cannulated and the opposite end of the vessel was completely sealed while being viewed with an inverted microscope. After verifying the absence of pressure leakage, we examined the vascular reactivity to various vasoactive agents under the fixed intravascular pressure (60 mm Hg). RESULTS: We found that the isolated mouse OAs were able to constrict in response to vasoconstrictors, including KCl, phenylephrine, endothelin-1, and prostaglandin PGH2. Moreover, this isolated vessel demonstrated vasodilation in a dose-dependent manner when vasodilatory agents, acetylcholine and bradykinin, were applied. CONCLUSION: Our findings suggest that the isolated olfactory artery would provide as a useful ex vivo model to study the molecular and cellular mechanisms of vascular function underlying cerebrovascular disorders and the direct effects of such disease-modifying pathways on cerebrovascular function utilizing pharmacological agents and genetically modified mouse models.

Cyclooxygenases, lipoxygenases, their targeted drugs and the prevention of Alzheimer's disease / 药学学报

Many studies have shown that chronic inflammation occurs in the brain of patients with Alzheimer's disease (AD). It is well known that long-term administration of non-steroidal anti-inflammatory drugs (NSAIDs) can alleviate the cognitive decline of AD patient and elderly. Several inflammatory cytokines produced in the metabolism of arachidonic acid (AA) are closely related to inflammatory diseases. Lipoxygenases (LOXs) and cyclooxygenases (COXs) play a crucial role in the AA network, the products eicosanoids have an important impact on the progression of AD. Although there are many arguments and conflicting evidence, currently LOXs and COXs are still the hot topics in the research on AD pathogenesis and drug development. Here, we review the progress in research on COXs and LOXs, including their actions on CNS and their association with AD, and explore the feasibility of LOXs and COXs as targets for the drugs to prevent and/or treat AD.

Microbiology of surgical site infections

Surgical site infections in the Philippines vary in frequency between second and third most common site of nosocomial infections. Most studies were concentrated on postoperative incisional surgical site infections with few reports on postoperative intra-abdominal and soft tissue infections, and practically no studies on other organ/space infections Infection rates varied from hospital to hospital with lowe infection rates reflected by surveillance methods based on microbiology culture reports and higher rates with active surveillance procedures. SLMC reported the lowest surgical wound infection rate at 0.12 percent while Jose Reyes Memorial Medical Center registered the highest rate at 14.4 percent. Postoperative intra-abdominal infection rate in one report was 2.3 percent. (PGH) while two other hospitals had 0.5 percent (STUH) and 1.0 percent (PGH) in another report. Traumatic nosocomial surgical infection rate was 21.43 percent and a superinfection rate in another study of 38.8 percent Majority of the hospitals had predominantly gram-negative organisms as etiologic agents in surgical site infections. In those hospitals where gram-positive organisms were the most fequently isolated organisms, the overall picture still showed that gran negative organisms were still the predominant group of organisms. The predominant gram-positive organisms were S. aureus and epidermidis while the predominant gram-negative organisms were Pseudomonas sp., E. coli, Proteus sp. and Enterobacter sp In the three hospitals where resistance patterns were reported, there was discordance in the results. Where one antibiotic may be useful in one hospital for a particular organism, it may not be an adequate drug for the other hospitals against the same organism. This underscores the fact that hospitals should have their own resistograms compiled by an active infection control committee which would serve as guides for initial antimicrobial therapy in surgical site infections.(Author)