Chronic caffeine intake increases androgenic stimuli,epithelial cell proliferation and hyperplasia in rat ventral prostate

Coffee intake has been associated with a low risk of developing cancer, including prostate cancer, which is one of the most commonly diagnosed cancer in men. However, few studies have evaluated the chronic effects of caffeine, which is the most abundant methylxanthine in coffee, on prostate morphology and physiology. In the present study, we investigated the effects of chronic, low‐dose caffeine intake on rat prostate morphology from puberty to adulthood. Five‐week‐old male Wistar rats were randomized into two experimental groups: caffeine‐treated (20 ppm in drinking water, n = 12) and control (n = 12). The ventral and dorsolateral prostates were dissected, weighted and submitted to morphological, morphometrical and immunohistochemical analysis of cellular proliferation, apoptosis and androgen receptor (AR) tissue expression. The testosterone (T) and dihydrotestosterone (DHT) concentrations were measured in the plasma. Our results show that caffeine intake increased the concentrations of T and DHT, organ weight, epithelial cell proliferation and AR tissue expression in the ventral prostatic lobe. All the ventral prostates from the caffeine‐treated animals presented various degrees of epithelial and stromal hyperplasia. Our results suggest that chronic caffeine intake from puberty increases androgenic signalling and cell proliferation in the rat prostate gland and can be related to the development of benign prostatic hyperplasia.     

Neonatal exposure to ethinylestradiol increases ventral prostate growth and promotes epithelial hyperplasia and inflammation in adult male gerbils

The aim of this study was to analyse morphologically the ventral prostate of adult Mongolian gerbils exposed to ethinylestradiol (EE) during the first week of postnatal development. Lactating females received daily, by gavage, doses of 10 μg/kg of EE diluted in 100 μl of mineral oil from the 1st to 10th postnatal day of the pups (EE group). In the control group (C), the lactating females received only the vehicle. Upon completing 120 days of age, the male offspring were euthanized and the prostates collected for analyses. We employed morphological, stereological‐morphometrical, immunohistochemical and ultrastructural methods. The results showed that the postnatal exposure to EE doubled the prostatic complex weight, increasing the epithelial and stromal compartments, in addition to the secretory activity of the ventral lobe of the prostate. All glands exposed to EE showed strong stromal remodelling, and some foci of epithelial hyperplasia and inflammatory infiltrate in both luminal and epithelial or stromal compartments. Cells positive for anti‐AR and anti‐PCNA reactions increased into the epithelial and stromal tissues. ERα‐positive cells, which are normally found in the stromal compartment of intact prostates, were frequently observed in the prostatic epithelium of treated animals. This study demonstrated that the exposure to EE during postnatal development causes histophysiological alterations in this gland, predisposing to the development of prostatic lesions during life. These results are important for public health, considering that women worldwide have commonly used EE. Moreover, the bioaccumulation of this chemical has increased in different ecosystems.     

Neuroendocrine and immune markers of maternal stress during pregnancy and infant cognitive development

Antenatal exposure to maternal stress is a factor that may impact on offspring cognitive development. While some evidence exists of an association between maternal antenatal depressive or anxiety symptoms and infants' cognitive outcomes, less is known about the role of biological indices of maternal antenatal stress in relation to infant cognitive development. The current study investigated the association between maternal depressive and anxiety symptoms, stress and inflammatory markers during pregnancy and infant's cognitive development in a sample of 104 healthy pregnant women (mean gestational age = 34.76; SD = 1.12) and their 12-week-old infants (mean postnatal weeks = 11.96; SD = 1.85). Maternal depressive and anxiety symptoms were evaluated during pregnancy, alongside measurements of serum Interleukin-6 (IL-6), C-Reactive Protein (CRP), salivary cortisol, and alpha amylase (sAA) concentrations. Infant cognitive development, maternal caregiving and concurrent anxiety or depressive symptoms were assessed 12 weeks after delivery. Hierarchical linear regressions indicated that higher maternal diurnal cortisol and CRP levels were independently associated with lower infant cognitive development scores, while adjusting for infant gender and gestational age, maternal IQ, caregiving, depressive, or anxiety symptoms. Though correlational, findings seem suggestive of a role for variation in maternal biological stress signals during pregnancy in influencing infants' early cognitive development.     

Foetal exposure to Panax ginseng extract reverts the effects of prenatal dexamethasone in the synthesis of testosterone by Leydig cells of the adult rat

The aim of this study was to examine the effect of maternal exposure to Panax ginseng extract (GE) on the prenatal dexamethasone (DEXA)‐induced increase in testosterone production by isolated Leydig cells in adult rats. Pregnant rats were treated with (i) GE (200 mg/kg) or vehicle on days 10–21; (ii) DEXA (100 μg/kg) or vehicle on days 14–21; or (iii) a combination of GE plus DEXA at the same doses and with the same regimen. Testosterone production was induced either by the activator of protein kinase A (dbcAMP) or substrates of steroidogenesis [22(R)‐hydroxycholesterol (22(R)‐OH‐C)] and pregnenolone. The capacity of rat Leydig cells exposed to DEXA to synthesize testosterone induced by dbcAMP, 22(R)‐OH‐C or pregnenolone was increased in comparison with the control group. Combined exposure to DEXA + GE prevented the effect of DEXA on the responsiveness of Leydig cells to all inductors of testosterone synthesis, whereas GE alone did not modify the response to inductors. No modifications in testosterone production were observed under basal conditions. StAR immunoexpression in Leydig cells was not modified by prenatal exposure to DEXA, GE or DEXA + GE. P450scc and glucocorticoid receptor immunoexpression was higher in offspring exposed to DEXA in comparison with the control group. This increased expression was prevented by combined treatment with DEXA + GE. The present findings demonstrate that GE is capable of reversing the effect of DEXA on testosterone synthesis by rat Leydig cells.     

Protective effect of γ‐tocopherol‐enriched diet on N‐methyl‐N‐nitrosourea‐induced epithelial dysplasia in rat ventral prostate

Despite recent advances in understanding the biological basis of prostate cancer (PCa), the management of this disease remains a challenge. Chemoprotective agents have been used to protect against or eradicate prostate malignancies. Here, we investigated the protective effect of γ‐tocopherol on N‐methyl‐N‐nitrosourea (MNU)‐induced epithelial dysplasia in the rat ventral prostate (VP). Thirty‐two male Wistar rats were divided into four groups (n = 8): control (CT): healthy control animals fed a standard diet; control+γ‐tocopherol (CT+γT): healthy control animals without intervention fed a γ‐tocopherol‐enriched diet (20 mg/kg); N‐methyl‐N‐nitrosourea (MNU): rats that received a single dose of MNU (30 mg/kg) plus testosterone propionate (100 mg/kg) and were fed a standard diet; and MNU+γ‐tocopherol (MNU+γT): rats that received the same treatment of MNU plus testosterone and were fed with a γ‐tocopherol‐enriched diet (20 mg/kg). After 4 months, the VPs were excised to evaluate morphology, cell proliferation and apoptosis, as well as cyclooxygenase‐2 (Cox‐2), glutathione‐S‐transferase‐pi (GST‐pi) and androgen receptor (AR) protein expression, and matrix metalloproteinase‐9 (MMP‐9) activity. An increase in the incidence of epithelial dysplasias, such as stratified epithelial hyperplasia and squamous metaplasia, in the MNU group was accompanied by augmented cell proliferation, GST‐pi and Cox‐2 immunoexpression and pro‐MMP‐9 activity. Stromal thickening and inflammatory foci were also observed. The administration of a γ‐tocopherol‐enriched diet significantly attenuated the adverse effects of MNU in the VP. The incidence of epithelial dysplasia decreased, along with the cell proliferation index, GST‐pi and Cox‐2 immunoexpression. The gelatinolytic activity of pro‐MMP‐9 returned to the levels observed for the CT group. These results suggest that γ‐tocopherol acts as a protective agent against MNU‐induced prostatic disorders in the rat ventral prostate.     

Corticosterone influences gerbil (Meriones unguiculatus) prostatic morphophysiology and alters its proliferation and apoptosis rates

Glucocorticoids (GCs) are hormones that are widely used in medicine; but although side effects are generally recognised, little is known about the precise mechanisms that is implicated in many of these side effects. Furthermore, GCs are highly correlated with stress and behaviour disorders. This study evaluated the effects of the glucocorticoid corticosterone on the ventral prostate of the Mongolian gerbil. Male gerbils (Meriones unguiculatus) (n = 5) received intraperitoneal injections of saline or corticosterone in doses of 0.5 mg/kg/day and 1.5 mg/kg/day for 5 days; while some of the animals were killed immediately after the treatment, the others were killed 5 days after the treatment period. The data show that corticosterone influences the structure and functionality of this organ. This hormone has anti‐proliferative and anti‐apoptotic properties in the prostate. In addition, the frequencies of the androgen (AR), oestrogen (ERα, ERβ) and glucocorticoid (GR) receptors changed. The frequencies of AR, GR and ERβ decreased in the Ct1/5 group; in the groups with rest period, the frequencies of GR increased and ERβ decreased in the epithelium. Changes in the proliferative index, apoptotic index and receptor activity may have contributed to the emergence of prostatic morphological alterations, such as the presence of cellular debris and inflammatory cells. Different doses of corticosterone had variable effects on the prostate, with a higher dose showing subtler effects and a lower dose showing more striking effects. The corticosterone effects on nuclear receptors were reverted or attenuated after a rest period, which was not observed for proliferation and apoptosis. In summary, we have demonstrated that corticosterone might influence the prostatic morphophysiology and that these changes may be linked in some way to the altered receptor distribution.     

Prenatal and perinatal factors associated with developing multiple sclerosis later in life: A systematic review and meta-analysis

ObjectiveBoth genetic and environmental factors play roles in Multiple Sclerosis (MS) etiopathogenesis. The relationship between prenatal/perinatal factors/exposures and future MS occurrence in the offspring remains controversial. Here, we aimed to review the available evidence on prenatal/perinatal factors associated with later MS occurrence.MethodWe performed systematic search of PubMed, Web of Science, and Scopus from inception to October 2020. We included original observational studies conducted on human participants addressing the association between prenatal/perinatal factors and MS occurrence. Data were extracted according to the PRISMA guideline. The adjusted odds ratio (OR) with 95% confidence interval (CI) was considered as the desired effect size. The heterogeneity was evaluated by Cochran's Q and I² and the publication bias was assessed. We excluded gestational/neonatal vitamin D level, season of birth, and latitude because of recently published systematic reviews/meta-analyses on these subjects.ResultsOverall, 2306 records were identified in the primary search. After excluding irrelevant studies, we evaluated 34 studies with contributing data on 100 prenatal/perinatal factors associated with an increased or decreased risk of MS occurrence. In the meta-analyses, we found no statistically significant associations between later MS occurrence in offspring and prenatal smoking exposure (OR = 1.01, 95% CI = 0.77–1.34), mode of delivery (OR = 0.90, 95% CI = 0.52–1.56), birth order (OR = 0.85, 95% CI = 0.72–1.00), and maternal age (OR = 1.34, 95% CI = 0.88–2.04). Paternal age and parents' marital status at the time of childbirth, maternal preeclampsia/ toxemia, forceps use, birth weight, plurality, and preterm birth were the other most studied factors, and none reported to affect MS risk.ConclusionWe found that prenatal smoking exposure, mode of delivery, birth order, and maternal age do not affect risk of future MS development. Moreover, most of the other investigated factors were reported not to affect MS risk in the offspring.     

Prenatal exposure to lipopolysaccharide results in cognitive deficits in age-increasing offspring rats

Studies have suggested that maternal infection/inflammation maybe a major risk factor for neurodevelopmental brain damage. In the present study, we evaluated the effects of prenatal exposure to a low level of inflammatory stimulation lipopolysaccharide (LPS) repeatedly on spatial learning and memory performances in rat offspring's lifetime. Sixteen pregnant Sprague–Dawley rats were randomly divided into two groups. The rats in the LPS group were treated i.p. with LPS (0.79 mg/kg) at gestation day 8, 10 and 12; meanwhile the rats in the control group were treated with saline. After delivery, the rat offspring at 3- (young), 10- (adult) and 20-mon-old (aged) were allocated. Spatial learning and memory abilities were tested by Morris water maze. The structure of hippocampal CA1 region was observed by light microscopy. The expression of synaptophysin (SYP) and glial fibrillary acidic protein (GFAP) in hippocampal CA1 region were measured by immunohistochemistry. Results showed that the rat offspring of LPS group needed longer escape latency and path-length in the Morris water maze and presented a significant neuron loss, decreased expression of SYP, increased expression of GFAP in CA1 region in histological studies. All these changes were more significant with the age increasing. These findings support the hypothesis that maternal systemic inflammation may alter the state of astrocytes in rat offspring for a long time, the alteration may affect neurons and synapse development in neural system, increase the neurons' vulnerability to environment especially as the age increasing, at last result in distinct learning and memory impairment.     

Prenatal prochloraz treatment significantly increases pregnancy length and reduces offspring weight but does not affect social-olfactory memory in rats

Metabolites of the commonly used imidazole fungicide prochloraz are androgen receptor antagonists. They have been shown to block androgen-driven development and compromise reproductive function. We tested the effect of prochloraz on cognitive behavior following exposure to this fungicide during the perinatal period. Pregnant Wistar rats were administered a 200 mg/kg dose of prochloraz on gestational day (GD) 7, GD11, and GD15. The social recognition test (SRT) was performed on 7-week-old male rat offspring. We found an increase in pregnancy length and a significantly reduced pup weight on PND15 and PND40 but no effect of prenatal prochloraz exposure on social investigation or acquisition of social-olfactory memory.     

Mitochondrial compromise in 3‐year old patas monkeys exposed in utero to human‐equivalent antiretroviral therapies

Antiretroviral (ARV) drug therapy, given during pregnancy for prevention of mother‐to‐child transmission of human immunodeficiency virus 1 (HIV‐1), induces fetal mitochondrial dysfunction in some children. However, the persistence/reversibility of that dysfunction is unclear. Here we have followed Erythrocebus patas (patas) monkey offspring for up to 3 years of age (similar in development to a 15‐year old human) after exposure of the dams to human‐equivalent in utero ARV exposure protocols. Pregnant patas dams (3–5/exposure group) were given ARV drug combinations that included zidovudine (AZT)/lamivudine (3TC)/abacavir (ABC), or AZT/3TC/nevirapine (NVP), for the last 10 weeks (50%) of gestation. Infants kept for 1 and 3 years also received drug for the first 6 weeks of life. In offpsring at birth, 1 and 3 years of age mitochondrial morphology, examined by electron microscopy (EM), was compromised compared to the unexposed controls. Mitochondrial DNA (mtDNA), measured by hybrid capture chemiluminescence assay (HCCA) was depleted in hearts of patas exposed to AZT/3TC/NVP at all ages (P < 0.05), but not in those exposed to AZT/3TC/ABC at any age. Compared to unexposed controls, mitochondrial reserve capacity oxygen consumption rate (OCR by Seahorse) in cultured bone marrow mesenchymal fibroblasts from 3‐year‐old patas offspring was ～50% reduced in AZT/3TC/ABC‐exposed patas (P < 0.01), but not in AZT/3TC/NVP‐exposed patas. Overall the data show that 3‐year‐old patas sustain persistent mitochondrial dysfunction as a result of perinatal ARV drug exposure. Environ. Mol. Mutagen. 57:526–534, 2016. © 2016 Wiley Periodicals, Inc.     

Differential expression of androgen and estrogen receptors in PCB (Aroclor 1254)-exposed rat ventral prostate: Impact of alpha-tocopherol

Polychlorinated biphenyls (PCBs) are environmental toxicants, which affect male fertility by altering the androgen and estrogen levels. PCB-induced toxic manifestations are associated with the production of reactive oxygen species. Vitamin E (α-tocopherol) is a major lipophilic chain breaking antioxidant, which protects polyunsaturated fatty acids in tissues against peroxidation, a property that could be beneficial in the male reproductive biology. The purpose of this study was to determine the impact of α-tocopherol on PCB (Aroclor 1254)-induced changes in androgen receptor (AR) and estrogen receptors (ERs) expression in Wistar rat ventral prostate. Rats were divided into 3 groups of 6 animals each. Group I rats were administered corn oil (vehicle) intraperitoneally (i.p.); Group II rats were treated with 2 mg kg^?1 day^?1 of PCB (i.p.); Group III rats were treated with 2 mg kg^?1 day^?1 of PCB (i.p.) along with simultaneous oral supplementation of 50 mg kg^?1 day^?1 of α-tocopherol. Serum testosterone and estradiol titers were assayed. Prostatic acid phosphatase activity (PAcP), citric acid concentration, generation of hydrogen peroxide (H₂O₂) and lipid peroxides (LPO) were estimated. mRNA and protein expression of AR, ER-α and ER-β in ventral prostate were quantified. Serum testosterone, estradiol, PAcP, citric acid levels, AR and ER-α expressions were significantly decreased while H₂O₂ generation, LPO, ER-β were increased in PCB-exposed animals. Simultaneous supplementation of α-tocopherol in PCB-exposed rats resulted in significant restoration of all the parameters to the control. The results suggest that α-tocopherol has definite protective effect against PCB-induced toxicity in ventral prostatic dysfunction.     

Maternal known drug allergy and long‐term dermatological morbidity of the offspring

Drug allergy is associated with adverse short‐term perinatal outcomes such as caesarian delivery and preterm delivery. The aim of the present study was to determine whether being born to a mother with known drug allergy increases the risk for long‐term dermatological morbidity of the offspring. A population‐based cohort study, comparing long‐term dermatological morbidity of offspring to mothers with and without known drug allergy, was conducted. Dermatological morbidity was assessed up to the age of 18 years according to a predefined set of ICD‐9 codes associated with hospitalization of the offspring. A Kaplan‐Meier survival curve was used to compare cumulative incidence of long‐term dermatological morbidity, and a Cox proportional hazards model was constructed to control of confounders. During the study period, 243,682 deliveries met the inclusion criteria, of them 4% (n = 9756) were of mothers with known drug allergy. Offspring born to mothers with known drug allergy had higher rates of long‐term dermatological morbidity Likewise, the cumulative incidence of long‐term dermatological morbidity was higher as compared with those without known drug allergy (Kaplan‐Meier log‐rank P = .021). Using a Cox proportional hazards model, controlling for confounders, being born to a mother with known drug allergy was found to be an independent risk factor for long‐term dermatological morbidity of the offspring (adjusted HR 1.2, 95% CI 1.03‐1.33, P = .016). Being born to a mother with known drug allergy is independently associated with higher risk for long‐term dermatological morbidity of the offspring.     

Prenatal exposure to ethinylestradiol alters the morphologic patterns and increases the predisposition for prostatic lesions in male and female gerbils during ageing

Ethinylestradiol (EE) is an endocrine disruptor (ED) which acts as an oestrogen agonist; this compound is known as an oral contraceptive. Male and female rodents exposed to EE during critical time points of development, such as in the prenatal period, show alterations in their reproductive tract during adulthood. Few studies have placed an emphasis on the effects of EE during ageing. Thus, this study had as it's objective the analysis of the morphological and immunohistochemical effects of exposure to EE in the prenatal period on ventral male prostate and female prostate of gerbils (Meriones unguiculatus) during ageing. The animals were exposed to EE (15 μg/kg/day) during the 18–22th days of prenatal life (EE/PRE group), and the analyses were performed when the male and female reached 12 months of age. Our results showed an increase in the development of prostatic intraepithelial neoplasia (PIN), which was observed in the male and female prostate of EE/PRE groups. Immunohistochemistry showed a rise in prostatic epithelial and basal cells immunoreactivity, respectively, and to AR and p63 in the male EE/PRE. There were alterations in the morphological pattern of the prostatic glands and increase in predisposition to emergence of prostatic lesions of both sexes during ageing. Despite male and female having been exposed to the same doses of EE, the “exposure to EE promoted modifications” more accentuated in the male prostate. Thus the male gland is more sensitive to the action of this synthetic oestrogen than the female prostate.     

Moderate prenatal ethanol exposure in the rat promotes kidney cell apoptosis,nephron deficits,and sex-specific kidney dysfunction in adult offspring

Alcohol during pregnancy can impair fetal development and result in offspring with neurodevelopmental deficits. Less is known about how low to moderate alcohol exposure can affect other organs, such as the kidney. Here, the effects of moderate ethanol exposure throughout pregnancy on kidney development were examined using a rat model. Rats were fed a liquid diet containing 6% ethanol (vol/vol) or control (0% ethanol) throughout pregnancy. Kidneys were collected at embryonic day (E) 20 or postnatal day (PN) 30 and total glomerular (nephron) number determined using unbiased stereology. Kidney function was examined in offspring at 8 and 19 months. At E20, fetuses exposed to ethanol had fewer nephrons with increased apoptosis. Alcohol exposure caused kidney dysregulation of pro- (Bax) and anti- (Bcl-2) apoptotic factors, and reduced expression of the cell proliferation marker, Ki67. Prenatal alcohol decreased expression of Gdnf and Tgfb1, important regulators of branching morphogenesis, in male fetuses. At PN30, kidney volume and nephron number were lower in offspring exposed to prenatal alcohol. Urine flow and osmolality were normal in offspring exposed to alcohol however sodium excretion tended to be lower in females prenatally exposed to alcohol. Findings suggest exposure to moderate levels of alcohol during pregnancy results in impaired kidney development and leads to a permanent nephron deficit. Although the impact on adult kidney function was relatively minor, these data highlight that even at moderate levels, alcohol consumption during pregnancy can have deleterious long-term outcomes and should be avoided.     

β-Adrenoceptor activation depresses brain inflammation and is neuroprotective in lipopolysaccharide-induced sensitization to oxygen-glucose deprivation in organotypic hippocampal slices

Background  

Inflammation acting in synergy with brain ischemia aggravates perinatal ischemic brain damage. The sensitizing effect of pro-inflammatory exposure prior to hypoxia is dependent on signaling by TNF-α through TNF receptor (TNFR) 1. Adrenoceptor (AR) activation is known to modulate the immune response and synaptic transmission. The possible protective effect of and AR activation against neuronal damage caused by tissue ischemia and inflammation, acting in concert, was evaluated in murine hippocampal organotypic slices treated with lipopolysaccharide (LPS) and subsequently subjected to oxygen-glucose deprivation (OGD).     

Exposure of pregnant rats to staphylococcal enterotoxin B increases offspring splenic Treg number and function via decreasing FoxP3 methylation

Staphylococcus aureus is an infectious pathogen that is relatively common, but that can cause severe disease in pregnant women and their fetus. We previously demonstrated that exposing pregnant rats to staphylococcal enterotoxin B (SEB) altered splenic CD4/CD8 T cell frequencies in their offspring. Whether prenatal SEB exposure impacts Tregs in these offspring, however, remains to be determined. As such, in this study, we intravenously injected pregnant rats with 15 μg of SEB on gestational day 16. Splenic tissue was then harvested from 1-, 3-, and 5-day-old neonatal rats and analyzed via flow cytometry to assess Treg numbers. In addition, FoxP3 expression levels were assessed via qPCR and western blotting, while FoxP3 methylation status was evaluated via methyl-DNA immunoprecipitation qPCR. Immunosuppression assays were additionally used to gauge Treg suppressive functionality. We found that exposing pregnant rats to SEB resulted in a significant increase in Treg numbers, FoxP3 expression, and Treg suppressive capacity in the spleens of both neonatal and adult offspring. In addition, total T cell, CD4⁺T cell, and non-Treg CD4⁺ T cell numbers were elevated in the spleens of offspring following prenatal SEB exposure. We additionally determined that SEB exposure resulted in a significant reduction in FoxP3 DNA methylation. Together, our results indicate that prenatal SEB exposure can markedly enhance offspring splenic Treg numbers and functionality at least in part by decreasing FoxP3 methylation.     

Prevalence of pollen‐induced allergic rhinitis with high pollen exposure in grasslands of northern China

Background

The aim of this study was to investigate the prevalence of epidemiologic and physician‐diagnosed pollen‐induced AR (PiAR) in the grasslands of northern China and to study the impact of the intensity and time of pollen exposure on PiAR prevalence.

Methods

A multistage, clustered and proportionately stratified random sampling with a field interviewer‐administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count.

Results

A total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05).

Conclusion

Pollen‐induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions.     

Effect of Prolactin on the Population of Epithelial Cells From Ventral Prostate of Intact and Cyproterone Acetate‐Treated Peripubertal Rats: Stereological and Immunohistochemical Study

The interactions between steroid and nonsteroid hormones in the prostate are of special interest during the growth phase of the gland. The purpose of this work is to study the influence of prolactin (PL), with or without androgenic blockade, on epithelial cells from peripubertal rat ventral prostate. Twenty male peripubertal Sprague‐Dawley rats were grouped as controls, or treated with cyproterone acetate (CA), CA plus PL (CA‐PL), or PL. The total number (N total) of epithelial cells, and their labeling indices to proliferative cell nuclear antigen (LI PCNA), apoptosis (LI apoptosis) and androgen receptors (LI AR) were measured. CA and PL treatment significantly decrease the N total, but the LI PCNA was unchanged. We have observed a greater LI apoptosis in pharmacologically castrated animals without PL than in the rats with androgenic blockade with PL. The LI AR does not change with CA treatment in the ventral region, but the PL significantly increases it. Androgenic blockade and PL decrease the number of epithelial cells from the ventral prostate. These changes are not attributable to the decrease of cell proliferation, rather to the increase of epithelial apoptosis. The increase of cells expressing AR after treatment with PL might be attributed to the decrease of testosterone secretion caused by the hyperprolactinemia. PL does not modulate the size of the ventral prostate in prepubertal rats. Anat Rec, 2009. © 2009 Wiley‐Liss, Inc.     

Genetic variants associated with drugs‐induced immediate hypersensitivity reactions: a PRISMA‐compliant systematic review

Drug hypersensitivity includes allergic (AR) and nonallergic reactions (NARs) influenced by genetic predisposition. We performed a systematic review of genetic predictors of IgE‐mediated AR and NAR with MEDLINE and PubMed search engine between January 1966 and December 2014. Among 3110 citations, the search selected 53 studies, 42 of which remained eligible. These eligible studies have evaluated genetic determinants of immediate reactions (IR) to beta‐lactams (n = 19), NAR against aspirin (n = 12) and other nonsteroidal anti‐inflammatory drugs (NSAIDs) (n = 8), and IR to biologics (n = 3). We reported two genomewide association studies and four case–control studies on candidate genes validated by replication. Genes involved in IR to beta‐lactams belonged to HLA type 2 antigen processing, IgE production, atopy, and inflammation, including 4 genes validated by replications, HLA‐DRA, ILR4, NOD2, and LGALS3. Genes involved in NAR to aspirin belonged to arachidonic acid pathway, membrane‐spanning 4A gene family, histamine production pathway, and pro‐inflammatory cytokines, while those involved in NAR to all NSAIDs belonged to arachidonic acid pathway and HLA antigen processing pathway. ALOX5 was a common predictor of studies on NAR to both aspirin and NSAIDs. Although these first conclusions could be drawn, this review highlights also the lack of reliable data and the need for replicating studies in contrasted populations, taking into account worldwide allele frequencies, gene–gene interactions, and contrasted situations of environmental exposure.