University of the Philippines Manila

About: University of the Philippines Manila is a education organization based out in Manila, Philippines. It is known for research contribution in the topics: Population & Medicine. The organization has 2218 authors who have published 2357 publications receiving 88781 citations. The organization is also known as: UPM.

Destruction of the hepatocyte junction by intercellular invasion of Leptospira causes jaundice in a hamster model of Weil's disease

Abstract: Leptospirosis is a zoonotic disease of global importance caused by pathogenic Leptospira Weil's disease is the most severe form of human leptospirosis, which is characterized by jaundice, haemorrhage and renal failure (Levett 2001; Bharti et al 2003) More than 50,000 cases of severe leptospirosis are reported each year with a case fatality rate higher than 10% (WHO 1999) Although jaundice has been one of the well-known symptoms of leptospirosis since its discovery, its mechanism still remains unknown Jaundice refers to the yellow discoloration of the sclerae, mucous membranes and skin and results from either enhanced bilirubin production or impaired bilirubin handling (uptake, conjugation or biliary excretion) by the liver (Roche & Kobos 2004) As jaundice is caused by dysfunctions at any steps of bilirubin metabolism, in some cases, it is difficult to elucidate its main mechanism Several kinds of bacterial infection are known to cause jaundice through a variety of mechanisms (Trauner et al 1998; Chand & Sanyal 2007) Leptospira are spiral-shaped, extremely thin bacteria They can bore through a gel-like medium in a cork-screw-like manner (Goldstein & Charon 1988) They are able to penetrate abraded skin and mucous membrane and migrate in host tissue (Bharti et al 2003) Several functional and histopathological studies on leptospirosis-related jaundice have been made on human patients (Ramos-Morales et al 1959; Arean 1962a; Kobayashi 2001; De Brito et al 2006) and experimental animals (Arean 1962b; Miller & Wilson 1966; Higgin & Cousineau 1977; Van den Ingh & Hartman 1986; Nally et al 2004) In human autopsies and animal models of acute Leptospira infection, hepatic cord disarray and dilation of intercellular space are commonly reported (Arean 1962a; Miller & Wilson 1966; De Brito et al 2006) Degenerative lesions, inflammation and necrosis are minimal (Nally et al 2004; De Brito et al 2006) Serum biochemical studies on human patients have demonstrated that concentrations of aspartate transaminase (AST) and alanine transaminase (ALT) are moderately increased, accompanied by minor increase in alkaline phosphatase (ALP) concentration (Ramos-Morales et al 1959; Kobayashi 2001) From these findings, most researchers have reported that impairment of bile excretion, intrahepatic cholestasis, is related to jaundice (Ramos-Morales et al 1959; Higgin & Cousineau 1977; Kobayashi 2001; Bharti et al 2003), but the mechanism is still unclear Moreover, there are few reports that correlated histopathological findings of liver with serum biochemical studies and localization of the organisms in leptospirosis or that examine the time course of histopathological changes and its association with leptospiral localization In this study, we examined the association between serum biochemical, histopathological changes and leptospiral localization during the development of jaundice in a hamster model of Weil's disease Hamsters inoculated with virulent Leptospira strains are used as animal models because their clinical manifestations and histopathological changes are similar to those of human leptospirosis (Haake 2006; Silva et al 2008) For scanning electron microscope (SEM) observation, freeze-cracking and cross-cutting methods were used to obtain three-dimensional images of the liver To investigate direct interactions between hepatocytes and the organism, hepatocyte couplets isolated from hamsters were co-cultured with either pathogenic or non-pathogenic leptospires

Do Pneumococcal Conjugate Vaccines Represent Good Value for Money in a Lower-Middle Income Country? A Cost-Utility Analysis in the Philippines

Abstract: Objectives The objective of this study is to assess the value for money of introducing pneumococcal conjugate vaccines as part of the immunization program in a lower-middle income country, the Philippines, which is not eligible for GAVI support and lower vaccine prices. It also includes the newest clinical evidence evaluating the efficacy of PCV10, which is lacking in other previous studies.

Inhibition of Human Immunodeficiency Virus Type 1 Replication in Latently Infected Cells by a Novel IκB Kinase Inhibitor

Abstract: In human immunodeficiency virus type 1 (HIV-1) latently infected cells, NF-κB plays a major role in the transcriptional induction of HIV-1 replication. Hence, downregulation of NF-κB activation has long been sought for effective anti-HIV therapy. Tumor necrosis factor alpha (TNF-α) stimulates IκB kinase (IKK) complex, a critical regulator in the NF-κB signaling pathway. A novel IKK inhibitor, ACHP {2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl-nicotinonitrile}, was developed and evaluated as a potent and specific inhibitor for IKK-α and IKK-β. In this study, we examined the ability of this compound to inhibit HIV-1 replication in OM10.1 cells latently infected with HIV. When these cells were pretreated with ACHP, TNF-α-induced HIV-1 replication was dramatically inhibited, as measured by the HIV p24 antigen levels in the culture supernatants. Its 50% effective concentration was approximately 0.56 μM, whereas its 50% cytotoxic concentration was about 15 μM. Western blot analysis revealed inhibition of IκBα phosphorylation, IκBα degradation, p65 nuclear translocation, and p65 phosphorylation. ACHP was also found to suppress HIV-1 long terminal repeat (LTR)-driven gene expression through the inhibition of NF-κB activation. Furthermore, ACHP inhibited TNF-α-induced NF-κB (p65) recruitment to the HIV-1 LTR, as assessed by chromatin immunoprecipitation assay. These findings suggest that ACHP acts as a potent suppressor of TNF-α-induced HIV replication in latently infected cells and that this inhibition is mediated through suppression of IKK activity.

Cultural beliefs on disease causation in the Philippines: challenge and implications in genetic counseling

Abstract: The provision of culturally competent health care is an important professional issue recognized by the pioneer genetic counselors in the Philippines. Being an archipelago consisting of 7,107 islands, the Philippines has approximately 175 ethnolinguistic groups with their own unique cultural identity and health practices. The emphasis on culture in our genetic counseling training recognizes its crucial role in molding an individual’s conceptualization of health, as well as other life aspects, especially since the Filipino culture is a mixture of indigenous as well as imported and borrowed elements. As part of this endeavor, we will describe in this paper seven common Filipino cultural beliefs: namamana, lihi, sumpa, gaba, pasma, namaligno, and kaloob ng Diyos. We will also share examples on how these common beliefs provide explanation as cause of illness and its implications in our genetic counseling profession.

Distribution of immunocompetent cells in decidua of controlled and uncontrolled (choriocarcinoma/hydatidiform mole) trophoblast invasion.

Abstract: Problem: Pregnancy has been considered as a model of successfully controlled tissue invasion where trophoblast cells infiltrate the maternal decidua without being rejected or without destroying the tissue. In choriocarcinoma (CC) and hydatidiform mole (HM), a dysregulation of invasive (malignant/benign) trophoblast cells is present. Immunocompetent cells (IC) are known to be involved in rejection pathways of malignant cells and can also be identified in early pregnancy decidua. The aim of the present study was to identify the phenotype of IC in decidua of women with normal pregnancy (NP), CC and HM. Methods: Immunocompetent cells were detected by immunohistochemistry in decidual tissue from first trimester NP (n = 10), CC (n = 12) and HM (n = 11) using antibodies against CD8+, CD3+, CD56+, CD68+ cell surface markers and mast cell tryptase (MCT). A scaled eye piece was used for cell counting to obtain semiquantitative results. Statistical analysis was performed using Wilcoxon rank/Mann–Whitney tests. Results: We observed a significantly increased number of lymphocytes positive for CD8, CD3 and MCT positive granulocytes in CC and HM compared with the samples from NP (all P ≤ 0.001). Lymphocytes positive for natural killer (NK) cell marker CD56 were significantly decreased in CC and HM versus NP (P ≤ 0.001). The number of CD68 positive cells (macrophages) were not significantly different among the tissue pools. Conclusion: The increase of CD8/CD3 T cells and mast cells in CC and HM and the decrease of CD56 cells, compared with NP, suggests the necessity of a balance between T and NK cells in controlling trophoblast invasion.