Inflammatory Responses in Blood Samples of Human Immunodeficiency Virus-Infected Patients with Pulmonary Infections

We analyzed the characteristics of the inflammatory response occurring in blood during pulmonary infections in human immunodeficiency virus (HIV)-infected patients. A prospective study of consecutive hospital admissions of HIV-infected patients with new-onset radiologic pulmonary infiltrates was carried out in a tertiary university hospital from April 1998 to May 2001. Plasma cyclic AMP receptor protein (CRP), interleukin 1β (IL-1β), IL-6, IL-8, IL-10, and tumor necrosis factor alpha (TNF-α) levels were determined at the time of admission and 4, 5, and 6 days later. Patients were included in a protocol addressed to study etiology and outcome of disease. A total of 249 episodes of infection were included, with the main diagnoses being bacterial pneumonia (BP) (118 episodes), Pneumocystis carinii pneumonia (PCP) (41 episodes), and mycobacteriosis (36 episodes). For these three patient groups, at the time of admission the median CRP and cytokine levels were as follows: CRP, 10.2, 3.8 and 5 mg/dl, respectively (P = 0.0001); IL-8, 19, 3, and 2.9 pg/ml (P = 0.045); and TNF-α, 46.4, 44, and 75 pg/ml, respectively (P = 0.029). There were no significant differences in levels of IL-1β, IL-6, or IL-10 among the patient groups. A total of 23 patients died. At the time of admission, HIV-infected patients with BP had higher plasma CRP and IL-8 levels than did PCP and mycobacteriosis patients. TNF-α levels were higher in patients with mycobacteriosis. An elevated IL-8 level (>61 pg/ml) at the time of admission was an independent factor associated with higher mortality (odds ratio, 12; 95% confidence interval, 1.2 to 235.5).     

Lutzomyia longipalpis salivary gland homogenate impairs cytokine production and costimulatory molecule expression on human monocytes and dendritic cells

In this report, we describe an investigation of the effects of Lutzomyia longipalpis sand fly salivary gland homogenates (SGH) on cytokine production and expression of costimulatory molecules on human monocytes, macrophages (Ms), and dendritic cells (DCs). SGH of L. longipalpis induced an increase in interleukin-6 (IL-6), IL-8 and IL-12p40 production but a decrease in tumor necrosis factor alpha and IL-10 production by lipopolysaccharida (LPS)-stimulated monocytes. We also examined the expression of costimulatory molecules on the surface of monocytes, Ms, and DCs. Whereas SGH affected the expression of these molecules on monocytes and Ms, it had little effect on these molecules on DCs. However, when DCs were generated from human monocytes in the presence of SGH, SGH inhibited the expression of costimulatory molecules. In addition, a decrease in the maturation of DCs induced by CD40L was observed in the presence of SGH. Finally, preincubating SGH with human sera containing anti-SGH-specific antibodies abolished the effects of SGH on cytokine production by LPS-stimulated monocytes.     

Impaired Recovery of CD4+ Cell Counts Following Highly Active Antiretroviral Therapy in Drug-Naïve Patients Coinfected with Human Immunodeficiency Virus and Hepatitis C Virus

Coinfection with the human immunodeficiency virus (HIV) and the hepatitis C virus (HCV) is highly prevalent in southern Europe. However, there are few and contradictory data about the effect of HCV carriage on the response to highly active antiretroviral therapy (HAART). In this study, the recovery of CD4+ T cells following HAART among antiretroviral-naïve patients seropositive for HIV with and without HCV coinfection was investigated. Two hundred one HIV-infected patients without previous exposure to antiretroviral drugs were included in the study. HCV coinfection was detected in 123 (61%) patients. The time to recover 200 CD4+ cells/µl was longer in the HCV-positive group (P<0.001). In a Cox model, HCV infection and lack of persistent HIV viremia (defined as <200 copies/ml) were associated with the time to recover 200 CD4+ cells/µl. The mean increase in CD4+ cell counts was lower in the HCV-positive group during the first year of therapy. HIV/HCV-coinfected patients naïve for antiretroviral therapy show a delayed recovery of CD4+ cell counts after starting HAART.     

Towards a Taenia solium cysticercosis vaccine: an epitope shared by Taenia crassiceps and Taenia solium protects mice against experimental cysticercosis

The Taenia crassiceps recombinant antigen KETc7 has been shown to be effective as a vaccine against experimental murine cysticercosis, a laboratory model used to test potentially promising molecules against porcine Taenia solium cysticercosis. Based on the deduced amino acid sequence of this proline-rich polypeptide, three fragments, GK-1, GK-2, and GK-3, were chemically synthesized in linear form. Of the three peptides, only GK-1 induced sterile protection against T. crassiceps cysticercosis in 40 to 70% of BALB/cAnN male mice. GK-1 is an 18-amino-acid peptide which contains at least one B-cell epitope, as demonstrated by its ability to induce an antibody response to the peptide and T. crassiceps antigen without need of a carrier protein. Immunofluorescence studies revealed that anti-GK1 antibodies strongly react with the native protein in the tegument of T. crassiceps and also with anatomical structures of T. solium eggs, oncospheres, cysticercus, and tapeworm. GK-1 also contains at least one T-cell epitope, capable of stimulating the proliferation of CD8(+) and to a lower extent CD4(+) T cells primed either with the free peptide or T. crassiceps total antigen. The supernatant of the stimulated cells contained high levels of gamma interferon and low levels of interleukin-4. Similar results were obtained with T cells tested for intracellular cytokine production, an indication of the peptide's capacity to induce an inflammatory response. The remarkable protection induced by GK-1 immunization, its physicochemical properties, and its presence in all developmental stages of T. solium point to this synthetic peptide as a strong candidate in the construction of a synthetic vaccine against T. solium pig cysticercosis.     

Histochemical localization of NADPH-diaphorase in neurons of the pheasant ileum

Localization patterns of NADPH-diaphorase-positive neurons in the pheasant ileum were investigated using an enzyme histochemical method. NADPH-diaphorase activity in the pheasant ileum was demonstrated in neuronal cells bodies and nerve fibres. The NADPH-diaphorase-positive nerve cells showed a polygonal shape and were present solitary or arranged in groups in the submucosal and muscular layers. Nerve fibres penetrated the wall of the ileum at its serosal surface, frequently in the vicinity of ileal arterial branches. They were abundantly present in muscular and submucosal layers of the ileum forming thicker nerves. Some nerve fibres traversed the submucosa into the lamina propria mucosae to form dense nerve plexuses. Fine nerve fibres were found to penetrate into intestinal villi encompassing the crypts underneath the epithelium. We conclude that the pheasant ileum is characterized by abundance of NADPH-diaphorase-positive nerve structures which may play a significant functional role in the small intestine of the pheasant.     

Connexin 26 mutations in cases of sensorineural deafness in eastern Austria

Mutations in the connexin 26 (Cx26) gene (GJB2) are associated with autosomal nonsyndromic sensorineural hearing loss. This study describes mutations in the Cx26 gene in cases of familial and sporadic hearing loss (HL) by gene sequencing and identifies the allelic frequency of the most common mutation leading to HL (35delG) in the population of eastern Austria. For this purpose we have developed and applied a molecular beacon based real-time mutation detection assay. Mutation frequencies in the Cx26 gene of individuals from affected families (14 out of 46) and sporadic cases (11 out of 40) were 30.4% and 27.5%, respectively. In addition to known disease related alterations, a novel mutation 262 G-->T (A88S) was also identified. 35delG accounted for almost 77% of all Cx26 mutations detected and displayed an allelic frequency in the normal hearing population of 1.7% (2 out of 120). The high prevalence of the 35delG mutation in eastern Austria would therefore allow screening of individuals and family members with Cx26 dependent deafness by a highly specific and semi-automated method.     

Principal components of mania

OBJECTIVE: An alternative to the categorical classification of psychiatric diseases is the dimensional study of the signs and symptoms of psychiatric syndromes. To date, there have been few reports about the dimensions of mania, and the existence of a depressive dimension in mania remains controversial. The aim of this study was to investigate the dimensions of manic disorder by using classical scales to study the signs and symptoms of affective disorders. METHODS: One-hundred and three consecutively admitted inpatients who met DSM IV criteria for bipolar disorder, manic or mixed were rated with the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HDRS-21). A principal components factor analysis of the HDRS-21 and the YMRS was carried out. RESULTS: Factor analysis showed five independent and clinically interpretable factors corresponding to depression, dysphoria, hedonism, psychosis and activation. The distribution of factor scores on the depressive factor was bimodal, whereas it was unimodal on the dysphoric, hedonism and activation factors. Finally, the psychosis factor was not normally distributed. LIMITATIONS: Patients of the sample were all medicated inpatients. CONCLUSIONS: Mania seems to be composed of three core dimensions, i.e. hedonism, dysphoria and activation, and is frequently accompanied by a psychotic and a depressive factor. The existence of a depressive factor suggests that it is essential to evaluate depression during mania, and the distribution of the depressive factor supports the existence of two different states in mania.