Drug-induced hyperprolactinemia: a case-non-case study from the national pharmacovigilance database

Hyperprolactinaemia is a relatively common endocrine abnormality caused by an increased secretion of prolactin from the pituitary gland. There are many causes of hyperprolactinaemia; drug therapy is a common cause in clinical practice. The present pharmacoepidemiological study conducted an analysis of the French Pharmacovigilance Database from January 1, 1985, to December 2000. We investigated the rates of hyperprolactinaemia according to therapeutic drug class, particularly where the Summaries of Product Characteristics (SPC) did not mention hyperprolactinaemia, and estimated the risk of developing hyperprolactinaemia during treatment. We calculated the odds ratio (OR) of reports associated with hyperprolactinaemia for all drugs. Of the 182,836 spontaneous adverse drug reactions reported to the French Pharmacovigilance network, 159 were hyperprolactinaemia. The sex ratio was 5.9 (136 women and 29 men), and mean age was 40 (range 14-85) years. Of the total number of adverse reactions, 31% were associated with neuroleptics, 28% with neuroleptic-like drugs, 26% with antidepressants, 5% with H2-receptor antagonists, and 10% with other drugs. Neuroleptics are not the only class of drugs for which hyperprolactinaemia is reported. Some drugs are clearly associated with an increased risk of hyperprolactinaemia, particularly the following: veralipride (OR = 108.7; IC 95%: 51.82-228), indoramin (OR = 78.68; IC 95%: 33.93-182.48), sertraline (OR = 15.74; IC 95%: 5.80-42.75), and ranitidine (OR = 4.43; IC 95%: 1.82-10.81). All these drugs are reported in the literature as inducing hyperprolactinaemia, although this adverse effect is not mentioned in the SPC. It is thus necessary to harmonise the SPC and encourage health professionals to notify all adverse reactions to their pharmacovigilance centres.     

Controlled ovarian hyperstimulation: a state of neutrophil activation

PROBLEM: To investigate if controlled ovarian hyperstimulation (COH) affects the expression of neutrophil adhesion molecules and if a correlation exists between neutrophil activation and serum sex-steroid levels. METHOD OF STUDY: The pilot study was carried out in the in vitro fertilization (IVF) unit of our department, and required no modification of our routine IVF protocol. Four patients arriving for baseline hormonal profile on day 1 of the menstrual cycle before initiation of COH (control group) and 11 patients admitted for oocyte recovery (study group) were included. Venous blood was obtained from all patients and examined for hormonal profile and neutrophil activation. The latter was performed by staining for the surface adhesion molecules beta2 integrin and L-selectin. Positive cell count and mean fluorescence intensity were determined by flow cytometry. RESULTS: While neutrophil L-selectin was significantly lower in the study group than in the control group, neutrophil beta2 integrin was nonsignificantly higher. Though no significant correlations were found between neutrophil adhesion molecules and patient age, serum estradiol level, and human chorionic gonadotropin level; neutrophil L-selectin was negatively correlated with serum progesterone levels. CONCLUSIONS: COH leads to neutrophil activation, which correlates with the degree of luteinization. Further studies are required to elucidate the relationship between the immune system and COH. These may lead to new strategies for promoting fertility and preventing complications of COH.     

Antidepressant-like effects of methanolic extract of <Emphasis Type="Italic">Bacopa monniera</Emphasis> in mice

Background

Bacopa monniera has been used as a cure for various ailments that include anxiety, epileptic disorders, dementia, blood purifier, cough and rheumatism, and some important local uses of the plant are in dermatitis, anemia, diabetes, promote fertility and prevent miscarriage for many years in Bangladesh. According to this background, the aim of the study was to evaluate the antidepressant-like effect of the methanolic extract of B. monniera (MEBM) in different behavioral models such as forced swimming test (FST), measurement of locomotor activity test (MLAT) and tail suspension test (TST) on mice after two weeks treatment.

Methods

Mice were divided into five groups (n?=?5/group): control group (deionized water), standard group where Imipramine hydrochloride (30 mg/kg) was used as standard drug and three test groups where three doses of the methanolic extract of B. monniera (MEBM) (50, 100, and 200 mg/kg) was used for two weeks treatment. All the drug and test samples were administered via gavage through oral route. To assess the antidepressant-like effect of MEBM forced swimming test (FST), tail suspension test (TST) and measurement of locomotor activity test (MLAT) have been done in mice.

Results

The results showed that a strong and dose-dependent antidepressant effects in different mice models. The main findings of the MEBM significantly reduced the duration of immobility times in the forced swimming test (p?<?0.001). Likewise, the extract significantly decreased the immobility time in the tail suspension test (p?<?0.001). Moreover, we employed an additional measurement of locomotor activity test to check the motor stimulating activity of the MEBM. The extract also significantly increased the locomotion, rearing and defecation effects in comparison to the control group (p?<?0.001).

Conclusion

The present results clearly demonstrate that the methanolic extract of B. monniera possesses antidepressant-like activity in the animal behavioral models. The current study warrants further investigation into identification of the active compounds in herbal medicines, in particular extract of B. monniera with antidepressant-like effects.

     

Plasma visfatin and retinol binding protein-4 levels in patients with type 2 diabetes mellitus and their relationship to adiposity and fatty liver

ObjectivesWe investigated whether plasma visfatin and binding protein-4 (RBP-4) levels correlate with obesity and type 2 diabetes mellitus (T2DM).Design and methodsTwo groups were enrolled: Group 1: 40 patients with T2DM and Group 2: 40 age- and gender-matched healthy controls. Both groups were subdivided according to body mass index (BMI) into non-obese (BMI < 25 kg/m²) and obese subjects (BMI ≥ 30 kg/m²) (20 each).ResultsPlasma visfatin and RBP-4 levels were significantly increased in T2DM patients compared with controls with similar BMI values (for both p < 0.001). Plasma visfatin and RBP-4 concentrations correlated with BMI, waist/hip ratio, insulin and homeostatic model assessment insulin resistance (HOMA_IR). Visfatin and RBP-4 correlated with visceral fat and liver fat in diabetic patients (for both p < 0.001).ConclusionVisfatin level was increased in T2DM, possibly related to hyperglycemia. Plasma RBP-4 correlated positively with liver fat and HOMA_IR which may reflect its effects on hepatic insulin sensitivity.     

Interferon-alpha Treatment for Disease Control in Metastatic Pheochromocytoma/Paraganglioma Patients

Interferon-alpha (IFN-alpha) is recommended in neuroendocrine tumors (NET). Malignant pheochromocytoma and paragangliomas (MPPGLs) constitute a rare subgroup of NET with few treatment options. IFN-alpha efficacy in patients with MPPGLs was evaluated in a single-center retrospective study. Progression-free survival (PFS) was the primary endpoint according to RECIST 1.1 and/or PERCIST 1.0, and response rate, safety, and symptomatic efficacy were secondary endpoints. Fourteen patients received peginterferon alfa-2a (90 to 180 μg/week) or interferon alfa-2b (1.5 to 3 million units × 3/week) at our institution between December 2005 and February 2014 as the first (n = 7), second (n = 3), or subsequent line (n = 4) of treatment. Most of the patients had a slowly progressive disease before IFN-alpha initiation. Eight patients were men (57%); the median age was 44. At the beginning of treatment, 12 patients had progressive disease demonstrated by FDG-PET (n = 9), MIBG (n = 1), or CT scan (n = 2). Most of the patients treated (64%) had metastatic disease limited to or predominantly located in the bones. During IFN-alpha therapy, bone-directed loco-regional treatments were performed in 9 patients (range 1–4). Median PFS was 17.2 months (95% CI [12.1–58.3]). We observed 3 partial metabolic responses, 9 stable diseases, and 2 progressive diseases. No partial response according to RECIST 1.1 was observed. Symptomatic relief of pain, headaches, diarrhea, or sweating occurred in 6 out of 10 symptomatic pts. Most frequent all grade IFN-α-related toxicities were asthenia (n = 10), lymphopenia (n = 7), thrombopenia (n = 6), and anemia (n = 5). Median overall survival was 7.5 years (95% CI [4–NR]). This study suggests symptomatic response and tumor control effect with interferon-alpha in progressive MPPGLs.     

Prognostic significance of fascin expression in advanced colorectal cancer: an immunohistochemical study of colorectal adenomas and adenocarcinomas

Background  

Fascin is an actin bundling protein with roles in the formation of cell protrusions and motility of mesenchymal and neuronal cells. Fascin is normally low or absent from epithelia, but is upregulated in several epithelial neoplasms where it may contribute to an invasive phenotype. Here, we report on the prevalence and potential clinical significance of fascin expression in relation to the progression of colorectal adenocarcinoma and to tumor cell proliferation as measured by Ki67 index.     

Retinal Sensitivity Correlates With the Superficial Vessel Density and Inner Layer Thickness in Diabetic Retinopathy

PurposeThe purpose of this paper was to present our study on the relationship between the parafoveal sensitivity measured using microperimetry and the vessel density (VD) assessed by optical coherence tomography-angiography (OCT-A) in eyes with diabetic retinopathy (DR).MethodsThe observational case series was conducted in a tertiary ophthalmology center. Eyes with DR and without macular edema were consecutively included. All eyes underwent microperimetry and OCT-A. The correlation between the regional retinal sensitivity and the corresponding local capillary changes and structural alterations seen on OCT-A was assessed in each retinal quadrant.ResultsThirty-seven eyes of 21 patients were included. The mean retinal sensitivity was 28.7 ± 2 decibel (dB). The mean parafoveal VD was 43.2 ± 4.2% in the superficial capillary plexus (SCP) and 48.1 ± 3.3% in the deep capillary complex (DCC). In the multivariate linear regression model, the mean retinal sensitivity was positively correlated with the VD in the SCP in the parafoveal ring (P = 0.01) and with the inner nuclear layer (INL) thickness (P = 0.01). The qualitative analysis of each quadrant showed the presence of areas of capillary dropout with a normal sensitivity. Conversely, all areas of decreased sensitivity (<25 dB) were associated with a decreased VD in the SCP and the DCC.ConclusionsThe parafoveal sensitivity positively correlated with the VD in the SCP in DR eyes. Areas with a low retinal sensitivity were always co-located with a loss of capillaries in the SCP and the DCC despite preserved outer retinal layers.     

The current Indian epidemic of superficial dermatophytosis due to Trichophyton mentagrophytes—A molecular study

The disease burden of chronic‐relapsing and therapy‐refractory superficial dermatophytosis dramatically increased in India within the past 5‐6 years. In order to evaluate the prevalence of this trend, 201 skin scrapings were collected from patients from all parts of India and were tested for dermatophytes using both fungal culture and a PCR‐ELISA directly performed with native skin scrapings. Fungal culture material was identified by genomic Sanger sequencing of the internal transcribed spacer (ITS) region and the translation elongation factor (TEF)‐1α gene. In total, 149 (74.13%) out of the 201 samples showed a dermatophyte‐positive culture result. Out of this, 138 (92.62%) samples were identified as Trichophyton (T.) mentagrophytes and 11 (7.38%) as Trichophyton rubrum. The PCR‐ELISA revealed similar results: 162 out of 201 (80.56%) samples were dermatophyte‐positive showing 151 (93.21%) T mentagrophytes‐ and 11 (6.79%) T rubrum‐positive samples. In this study, we show for the first time a dramatic Indian‐wide switch from T rubrum to T mentagrophytes. Additionally, sequencing revealed a solely occurring T mentagrophytes “Indian ITS genotype” that might be disseminated Indian‐wide due to the widespread abuse of topical clobetasol and other steroid molecules mixed with antifungal and antibacterial agents.