Chronic exposure to cigarette smoke transiently worsens the disease course in a mouse model of pulmonary paracoccidioidomycosis

ABSTRACT Paracoccidioidomycosis (PCM) may present as an acute/subacute clinical form, characterized by a progressive disease arising from the airborne initial infection, or, most often, as an asymptomatic or subclinical infection that may manifest later during an individual's life, the chronic form. Epidemiological studies show the existence of a strong association between smoking and the development of the chronic form. Current evidence demonstrates that cigarette smoke (CS) has immunosuppressive properties that could be implicated in the increasing susceptibility to the chronic form of PCM. To address this issue, we developed a murine model of a non-progressive pulmonary form of PCM that was exposed to CS at a magnitude that mimicked a moderate smoker. The chronic CS exposure started after 2 weeks and lasted up until 20 weeks post-infection, with the aim of mimicking human natural history, since it is estimated that individuals from endemic areas are infected early in life. The control group consisted of infected but not CS-exposed mice. We assessed the lung fungal burden (colony forming units [CFU]) and the area affected by the granulomatous inflammatory response, fungal dissemination to spleen and liver, and, by immunohistochemistry, the presence of CD4 and CD8 lymphocytes, CD68 and MAC-2 macrophages, and IFN-γ, IL-10 and TNF expressing cells within the granulomatous response. We detected a CS effect as early as 2 weeks after exposure (four weeks post-infection) when the lung CFU of exposed animals was significantly higher than in their non-exposed counterparts. At 12 weeks, the CS-exposed animals presented a more severe disease, as witnessed by the persistent higher lung fungal load (although it did not reach statistical significance [ p = 0.054]), greater dissemination to other organs, greater affected area of the lung, decreased IFN-γ/IL-10 ratio, and higher TNF expression within the granulomas, compared with CS-non-exposed mice. The number of CD4 and CD8 lymphocytes infiltrating the granulomas was similar between both mice groups, but there was a decrease in the number of MAC-2+ macrophages. No difference was noted in the CD68+ macrophage number. However, the follow-up in week 20 showed that the immunological effects of exposure to CS ceased, with both CS and NCS mice showing the same infectious features, i.e., a trend for resolution of the infection. In conclusion, we show that chronic CS-exposure alters the course of the disease in an experimental model of subclinical pulmonary PCM, confirming the epidemiological link between CS-exposure and the chronic form of PCM. However, we also show that this effect is transitory, being detected between 4- and 12-weeks post-infection but not thereafter. The possible immune mechanisms that mediate this effect and the reasons for its transitory effect are discussed.

Clinical Observation of Recombinant Human Interferon α2b Vaginal Effervescent Capsules Combined with Radiofrequency Ablation in the Treatment of Cervical Erosion Combined with HPV Subclinical Infection / 中国药房

OBJECTIVE:To investigate the clinical efficacy and safety of Recombinant human interferon α2b(rhIFN α2b) vaginal effervescent capsules combined with radiofrequency ablation in the treatment of cervical erosion with human papilloma virus (HPV)subclinical infection(SPI). METHODS:A total of 207 cervical erosion patients with SPI were selected from gynecology outpatient department of our hospital during Jul. 2014-Aug. 2015 and then divided into group A,B,C according to random number table,with 69 cases in each group. Group A was given rhIFN α2b vaginal effervescent capsules 800 thousand IU,via posterior for-nix,qd,3 days after the end of menstruation,10 days as a treatment course,for 3 courses. Group B received radiofrequency abla-tion. Group C was given constant dose of rhIFN α2b vaginal effervescent capsules combined with radiofrequency ablation. The clini-cal efficacy of 3 groups,the rate of wound healing,the rate of associated symptoms disappearance 2 weeks after surgery and the in-cidence of complications in group B and C were evaluated. The occurrence of ADR was recorded. RESULTS:The response rates of group B,C were 94.20% and 98.55%,which were significantly higher than 62.32% of group A. The response rates of SPI in group C was 92.75%,which was significantly higher than 63.77% of group B,with statistical significance(P0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:rhIFN α2b vaginal effervescent capsules combined with radiofrequency ablation can effective-ly improve the efficacy of cervical erosion with SPI,shorten the wound healing time with good safety.

Potential biomarkers as an indicator of vertical transmission of Johne's disease in a Korean native cattle farm

Paratuberculosis (PTB) is caused by Mycobacterium avium subsp. paratuberculosis (MAP) and is one of the most widespread and economically important diseases in cattle. After birth, calves are raised with natural breast feeding without separation from their mothers in most Korean native cattle (Hanwoo breed) farms. Vertical transmission of PTB has been reported, but the exact PTB infection route has not been revealed in Hanwoo farms. Calves of MAP seropositive dams were tested for MAP presence and MAP antibodies in feces and tissues. MAP was detected in calf tissues by using polymerase chain reaction. Expressions of genes reported to be prognostic biomarkers of MAP infection changed in both calves and cows (p < 0.05). Expression of two genes (HGF and SERPINE1) were significantly decreased in MAP-infected cattle and their offspring (p < 0.01). The results suggest that biomarker gene expression profiles can be useful in detecting early stage MAP infection. Based on the results, complete eradication of MAP may be possible if accurate diagnostic methods to detect infected calves are added to the current PTB eradication strategy, which, because infected individuals are likely to develop into fecal MAP shedders at any time, includes isolation of new born calves and feeding sterilized colostrum.

Recombinant Human Interferon α-2b Vaginal Effervescent Capsules Combined with Matrine Gels in the Treatment of Cervical Human Papilloma Virus (HPV) Subclinical Infection / 中国药师

Objective:To discuss the curative effect and security of recombinant human interferon α-2b vaginal effervescent capsules combined with matrine gels in the treatment of cervical human papilloma virus ( HPV) subclinical infection. Methods:Totally 74 cases of patients with cervical HPV subclinical infection were selected and divided into the observation group (n = 37) and the control group (n = 37) at random. The patients in the observation group were given recombinant human interferon α-2b vaginal effervescent capsules combined with matrine gels, while the patients in the control group were only given recombinant human interferon α-2b vaginal effervescent capsules for 3 treatment courses. The clinical curative effect and adverse reactions in the two groups after the medical treatment were observed, and the clinical curative effect in the 6-month follow-up after the medical treatment was observed and compared. Results:After the 3-month treatment, the total clinical efficiency in the observation group was much higher than that in the control group (P 0. 05). Six-month follow-up was performed and the total clinical efficiency in the observation group was much higher than that in the control group (P < 0. 05). Conclusion:Recombinant human interferon α-2b vaginal effervescent capsules combined with matrine gels have reliable curative effect on cervical HPV subclinical infection with high security and reliable long-term follow-up efficacy, which is benefit for the reoccurrence control of the disease.

Deficiencia de hierro y anemia en escolares residentes de gran altitud: asociación con infección / Iron deficiency and anemia in high altitude school children: association with infection

Pregunta de investigación: ¿Cuál será la asociación entre la deficiencia de hierro y anemia, e infecciones en niños escolares de zona periférica de La Paz, Bolivia, residentes de altitud, en la gestión 2011? Objetivo: Establecer la asociación entre la deficiencia de hierro y anemia, e infecciones en niños escolares de zona periférica de La Paz, Bolivia, residentes de altitud, en la gestión 2011...

Research Question: What is the association between iron deficiency, anemia and infections in high altitude residents school children in peripheral areas of La Paz city, Bolivia, 2011? Objective: To determinate the association between iron deficiency, anemia and infections in high altitude residents school children in peripheral areas of La Paz city, Bolivia, 2011...

Human papillomavirus prevalence in the genital tract of asymthomatic men: virological ans epidemiological aspects / Prevalência da infecção por papilomavírus humano no trato genital de homens assintomáticos: aspectos virológicos e epidemiológicos

Currently, genital tract infection by human papillomavirus (HPV) is the most prevalent sexually transmitted virosis in the world. However, there are stillgaps in knowledge regarding the etiology of penile cancer, and the pathogenic processes of HPV in men are not completely understood, especially in cases ofsubclinical infections. This study aimed to determine the prevalence of HPV infection in penile swab samples, derived from a clinically asymptomatic malepopulation. For this purpose, 261 samples were analysed, collected between 2010 and 2013 in different institutions of the city of Rio de Janeiro, includinghospitals , a laboratory of clinical analysis, and a metallurgical company...

Atualmente, a infecção do trato genital pelo papilomavírus humano (HPV) é uma das viroses sexualmente transmissíveis mais prevalentes do mundo. Entretanto, ainda existem lacunas de conhecimento a respeito da citologia do câncer de pênis, e os processos patogênicos do HPV no homem ainda não estão totalmente elucidados, principalmente nos casos de infecções subclínicas. Este estudo teve como objetivo determinar a prevalência da infecção por HPV em amostras de esfregaços de pênis, oriundos de uma população masculina clinicamente assintomática. Para tanto, foram analisadas 261 amostras, coletadas entre 2010 e 2013 em diferentes instituições na cidade do Rio de Janeiro, incluindo hospitais, um laboratório de análises clínicas e, uma empresa metalúrgica...

High rates of undiagnosed leprosy and subclinical infection amongst school children in the Amazon Region

Leprosy in children is correlated with community-level factors, including the recent presence of disease and active foci of transmission in the community. We performed clinical and serological examinations of 1,592 randomly selected school children (SC) in a cross-sectional study of eight hyperendemic municipalities in the Brazilian Amazon Region. Sixty-three (4%) SC, with a mean age of 13.3 years (standard deviation = 2.6), were diagnosed with leprosy and 777 (48.8%) were seropositive for anti-phenolic glycolipid-I (PGL-I). Additionally, we evaluated 256 house-hold contacts (HHCs) of the students diagnosed with leprosy; 24 (9.4%) HHC were also diagnosed with leprosy and 107 (41.8%) were seropositive. The seroprevalence of anti-PGL-I was significantly higher amongst girls, students from urban areas and students from public schools (p < 0.0001). Forty-five (71.4%) new cases detected amongst SC were classified as paucibacillary and 59 (93.6%) patients did not demonstrate any degree of physical disability at diagnosis. The results of this study suggest that there is a high rate of undiagnosed leprosy and subclinical infection amongst children in the Amazon Region. The advantages of school surveys in hyperendemic areas include identifying leprosy patients at an early stage when they show no physical disabilities, preventing the spread of the infection in the community and breaking the chain of transmission.

First encounter of subclinical human Leishmania (Viannia) infection in State of Rio Grande do Sul, Brazil

The objective of the present study was to evaluate the specificity of the Montenegro skin test (MST) in an area in Brazil, state of Grande do Sul State (RS), which was considered to be non-endemic for leishmaniasis. Sixty subjects presented a positive MST and were reevaluated by clinical examination, serology and polymerase chain reaction (PCR) of peripheral blood for the detection of subclinical Leishmania infection. None of the subjects presented clinical signs or symptoms of current leishmaniasis or a history of the disease.Leishmania (Viannia) DNA was detected in blood by PCR and hybridization in one subject. The PCR skin test-positive individual remained asymptomatic throughout the study. Clinical examination showed no scars suggestive of past cutaneous leishmaniasis. Human subclinical infection with Leishmania (Viannia) in RS was confirmed by PCR. This is the first report of subclinical infection with this parasite in the human population of this area.

Detection of betanodaviruses in apparently healthy aquarium fishes and invertebrates

Betanodaviruses are the causative agents of viral nervous necrosis (VNN) in cultured marine fish. A total of 237 apparently healthy aquarium fish, marine (65 species) and freshwater (12 species) fishes and marine invertebrates (4 species), which were stocked in a commercial aquarium in Seoul, South Korea, were collected from November 2005 to February 2006. The brains of the fish and other tissues of the invertebrates were examined by reverse transcriptasepolymerase chain reaction (RT-PCR) and nested PCR to detect betanodavirus. Positive nested PCR results were obtained from the brains of 8 marine fish species (shrimp fish Aeoliscus strigatus, milkfish Chanos chanos, three spot damsel Dascyllus trimaculatus, Japanese anchovy Engraulis japonicus, pinecone fish Monocentris japonica, blue ribbon eel Rhinomuraena quaesita, look down fish Selene vomer, yellow tang Zebrasoma flavesenes), 1 marine invertebrate species (spiny lobster Pamulirus versicolor), and 2 freshwater fish species (South American leaf fish Monocirrhus polyacanthus and red piranha Pygocentrus nattereri). The detection rate in nested PCR was 11/237 (4.64%). These subclinically infected aquarium fish and invertebrates may constitute an inoculum source of betanodaviruses for cultured fishes in the Korean Peninsula.

Clinical value of human papillomavirus genotype distribution in HPV infection / 第三军医大学学报

Objective To analyze the distribution of human papillomavirus (HPV) genotype in the diseases associated with HPV infection and explore the role of HPV genotype in these diseases. Methods Retrospective analysis was carried out to compare HPV genotypes of 353 outpatients suffering the diseases associated with HPV infection including cervical caner,cervical intraepithelial neoplasia (CIN),genital duc condyloma,and subclinical cervical human papillomavirus infection (SPI) in our department from January to October 2008. HybriMax were used to detect HPV genotype. The distribution data of HPV genotype were statistically analyzed. Results Totally 176 HPV positive females were found with a positive rate of 49.86%. HPV positive rate in cervical cancer was 100%,and all of them were high risk HPV. The positive rate was increased with the severity of CIN,and the higher histological-grade was,the higher HPV positive rate was (P

CERTAIN ASPECTS REGARDING CHRONIC SUBCLINICAL HEPATITIS B VIRUS INFECTION / 解放军医学杂志

Infection rate of HBV in the high-risk population, such as dentists and the patients undertaking hemodialysis, was not higher than those in general population. The occurrence of the subclinical infection state might be resulted from hypo-responsiveness of humoral and cellular immunity to HBsAg. Of 257 cases of liver biopsy, 44% of them were diagnosed as chronic hepatitis of various categories. No relationship was found between the expression patterns of viral antigens and the inflammatory activity in the liver. The infection state was quite stable. HBeAg/anti-HBe seroconversion was not a turning point from replicative to nonreplicative phase of the virus. The individuals with intrahepatic integrated HBV DNA might be the genome carriers with sero-negative HBsAg. The above results illustrate the characteristics of hyporesponsive HBV infection in hyperendemic area in China.