Differences in vulnerability to nicotine-induced kindling between female and male periadolescent rats

Rationale

It has recently been reported that chronic nicotine administration at subconvulsive doses causes seizures, a phenomenon referred to as kindling. Evidence points to the involvement of oxidative stress in pharmacological and electrical kindling, sex is known to influence the brain’s response to nicotine.

Objectives

This study investigated the sex differences in vulnerability to nicotine-induced kindling and the involvement of oxidative stress in this phenomenon.

Methods

Male and female periadolescent Wistar rats received repeated injections of a subconvulsive dose of nicotine (hemisulfate salt; 2 mg/kg, i.p.) every weekday for up to 25 days. To better understand the influence of oxidative stress in nicotine kindling, the antioxidant vitamin E (200 and 400 mg/kg, p.o.) was administered prior to nicotine administration. The levels of gluthatione (GSH), superoxide dismutase (SOD) activity, and lipid peroxidation were determined in the hippocampus (HC), prefrontal cortex (PFC), and striatum.

Results

Female animals developed kindling more rapidly than male rats. In female rats, kindling was associated with decreases in antioxidant defenses, including GSH levels in the HC and striatum and SOD activity in the PFC and striatum, and increased lipid peroxidation in all brain areas studied. By contrast, male kindled animals presented only with a decrease in the GSH in the HC. Vitamin E prevented the occurrence of kindled seizures by 80 % and 75 % in male and female rats, respectively.

Conclusion

These novel findings indicate that female periadolescent rats develop nicotine-kindled seizures earlier than their male counterparts. Differences in the oxidative balance may be involved in this mechanism.     

The Histone Demethylase PHF8 Governs Retinoic Acid Response in Acute Promyelocytic Leukemia

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Highlights? Histone demethylase PHF8 is recruited by PML-RARα upon ATRA treatment in APL ? Enzymatic activity and serine phosphorylation of PHF8 are required for ATRA response ? Activation of PHF8 confers ATRA sensitivity to resistant APL cells in vivo ? Pharmacological inhibition of PHF8 dephosphorylation sensitizes ATRA-resistant cells     

Epidemiological aspects of melanoma at a university hospital dermatology center over a period of 20 years

BACKGROUND

The incidence of melanoma has been steadily rising in past decades. Although it accounts for only 3% of all skin cancers, it is responsible for 75% of deaths.

OBJECTIVE

to describe the epidemiological aspects of melanoma in a university hospital setting over a period of 20 years.

METHODS

A total of 166 patients were analyzed between January 1990 and January 2010 for clinical and histological variables and correlations between them. A 5% level of significance was adopted.

RESULTS

The majority of patients were Caucasians (74%), females (61%), with a mean age at diagnosis of 55. The predominant histological type was lentigo maligna/lentigo maligna melanoma (35.7%) and the head and neck was the most affected site (30.7%). Among non-Caucasians, the acral region was the most affected. Most tumors were in situ (41.1%). Growth of the lesion was the most frequent complaint (58.1%) and bleeding was most frequently associated with melanomas with a depth > 4mm. There were seven deaths (4.2%), with a high risk among men, non-Caucasians and those under 20 years of age, with a Breslow''s depth > 2mm, with lentiginous acral melanoma and with a history of growth and bleeding.

CONCLUSIONS

Our sample differs from most of the studies in the predominant location (head and neck), histological type (lentigo maligna/ lentigo maligna melanoma) and a major risk of death under the age of 20, which could be with a reflex of regional variation. Broader studies are necessary for validation of the results.     

Matrigel-embedded 3D culture of Huh-7 cells as a hepatocyte-like polarized system to study hepatitis C virus cycle

Hepatocytes are highly polarized cells where intercellular junctions, including tight junctions (TJs), determine the polarity. Recently, the TJ-associated proteins claudin-1 and occludin have been implicated in hepatitis C virus (HCV) entry and spread. Nevertheless, cell line-based experimental systems that exhibit hepatocyte-like polarity and permit robust infection and virion production are not currently available. Thus, we sought to determine whether cell line-based, Matrigel-embedded cultures could be used to study hepatitis C virus (HCV) infection and virion production in a context of hepatocyte-like polarized cells. In contrast to standard bidimensional cultures, Matrigel-cultured Huh-7 cells adopted hepatocyte polarization features forming a continuous network of functional proto-bile canaliculi structures. These 3D cultures supported HCV infection by JFH-1 virus and produced infective viral particles which shifted towards lower densities with higher associated specific infectivity. In conclusion, our findings describe a novel use of Matrigel to study the entire HCV cycle in a more relevant context.     

Novel association of acid phosphatase locus 1*C allele with systemic lupus erythematosus

The red cell acid phosphatase (ACP1) gene, which encodes a low-molecular-weight phosphotyrosine phosphatase, has been suggested as a common genetic factor of autoimmunity. In the present study, we aim to investigate the possible association of ACP1 with the susceptibility of systemic lupus erythematosus (SLE). A total of 1,546 SLE patients and 1,947 healthy individuals from 4 Caucasians populations were included in the present study. Four single-nucleotide polymorphisms (SNPs) were genotyped in this study: rs10167992, rs11553742, rs7576247, and rs3828329. ACP1*A, ACP1*B, and ACP1*C codominant ACP1 alleles were determined using 2 of the SNPs and analyzed. After the meta-analysis test was performed, a significant association of rs11553742*T was observed (p_pooled = 0.005, odds ratios = 1.37 [1.10-1.70]), retaining significance after multiple testing was applied (p_FDR = 0.019). Our data indicate for first time the association of rs11553742*T with increased susceptibility in SLE patients.     

Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages

Langerhans cells (LCs) are the dendritic cells (DCs) of the epidermis, forming one of the first hematopoietic lines of defense against skin pathogens. In contrast to other DCs, LCs arise from hematopoietic precursors that seed the skin before birth. However, the origin of these embryonic precursors remains unclear. Using in vivo lineage tracing, we identify a first wave of yolk sac (YS)-derived primitive myeloid progenitors that seed the skin before the onset of fetal liver hematopoiesis. YS progenitors migrate to the embryo proper, including the prospective skin, where they give rise to LC precursors, and the brain rudiment, where they give rise to microglial cells. However, in contrast to microglia, which remain of YS origin throughout life, YS-derived LC precursors are largely replaced by fetal liver monocytes during late embryogenesis. Consequently, adult LCs derive predominantly from fetal liver monocyte-derived cells with a minor contribution of YS-derived cells. Altogether, we establish that adult LCs have a dual origin, bridging early embryonic and late fetal myeloid development.     

Clinical significance of Candida colonization of intravascular catheters in the absence of documented candidemia

In order to assess the significance of Candida colonization of intravascular catheters (IVC) in patients without documented candidemia, we retrospectively reviewed all Candida-positive IVC tip cultures over a 4-year period. Cases were defined as those with a culture yielding ≥15 colony-forming units of Candida spp. that either did not have blood cultures (BC) taken or had concomitant BC negative for Candida. Patients were followed up until death or 8 months after discharge. Risk factors for poor outcome following IVC removal (death, candidemia, or Candida-related complication) were analyzed. We analyzed a total of 40 patients. Overall mortality was 40.0%, with no death directly attributed to Candida infection. Twenty-two patients received antifungal therapy at the time of IVC removal. Only 1 patient developed a metastatic complication (chorioretinitis) attributable to transient candidemia (2.5% of the global cohort and 3.7% among those with concomitant BC). There were no cases of subsequent candidemia. In the multivariate analysis, the use of antifungal therapy did not show any impact on the risk of poor outcome. The risk of invasive disease in patients with isolated IVC colonization by Candida seems to be low. Nevertheless, the initiation of systemic antifungal therapy should be carefully considered in such context.