Risk of Guillain-Barré syndrome after 2010–2011 influenza vaccination

Influenza vaccination has been implicated in Guillain Barré Syndrome (GBS) although the evidence for this link is controversial. A case–control study was conducted between October 2010 and May 2011 in seven Italian Regions to explore the relation between influenza vaccination and GBS. The study included 176 GBS incident cases aged ≥18 years from 86 neurological centers. Controls were selected among patients admitted for acute conditions to the Emergency Department of the same hospital as cases. Each control was matched to a case by sex, age, Region and admission date. Two different analyses were conducted: a matched case–control analysis and a self-controlled case series analysis (SCCS). Case–control analysis included 140 cases matched to 308 controls. The adjusted matched odds ratio (OR) for GBS occurrence within 6 weeks after influenza vaccination was 3.8 (95 % CI: 1.3, 10.5). A much stronger association with gastrointestinal infections (OR = 23.8; 95 % CI 7.3, 77.6) and influenza-like illness or upper respiratory tract infections (OR = 11.5; 95 % CI 5.6, 23.5) was highlighted. The SCCS analysis included all 176 GBS cases. Influenza vaccination was associated with GBS, with a relative risk of 2.1 (95 % CI 1.1, 3.9). According to these results the attributable risk in adults ranges from two to five GBS cases per 1,000,000 vaccinations.     

Comparison of the chemical composition and biological effects of the roots,branches and leaves of Heteropterys tomentosa A. Juss

Ethnopharmacological relevance: Heteropterys tomentosa

A. Juss (Malpighiaceae), commonly mistaken as Heteropterys aphrodisiaca, is chronically used by the Brazilian population to improve general health due to its claimed protective effects against a wide range of medical conditions.

Aim of the study

This study in rodents aimed to verify the adaptogenic potential of the hydroalcoholic extracts of the roots (the most commonly used portion), branches and leaves of the plant.

Materials and methods

The phytochemical constitution of the extracts was analyzed through thin-layer chromatography and high-performance liquid chromatography. Restriction- and cold-induced stress in rats treated for 14 days with 100 or 300 mg/kg of the extracts were used to evaluate parameters such as ulceration, adrenals, thymus and spleen weights, as well as ACTH and corticosterone plasmatic levels. The stress response also was evaluated in mice by self-analgesia induced by restraint stress, after 7 days of treatment at doses of 100 and 300 mg/kg. The learning and memory of aged rats treated with extracts of root or branches at the dose of 50 mg/kg for 80 days were evaluated in the elevated T-maze test.

Results

The chemical constituents of the three parts of the plant were relatively similar in the presence of saponins, hydrolysable tannins, flavonoids, polyphenols and triterpenes. None of the three extracts were capable of protecting the stomach from ulcerations in rats submitted to cold restraint stress or protecting from alterations in adrenal or spleen weight (p>0.05). Furthermore, the extracts did not inhibit increases in plasma levels of corticosterone and adrenocorticotropic hormone. Moreover, the extracts did not inhibit self-analgesia induced by restraint stress in mice and did not improve the performance of aged rats in the T-maze test (p>0.05).

Conclusion

The tests employed in this study did not show evidence of adaptogenic activity in the three extracts of Heteropterys tomentosa.     

Tryptophan oxidation by singlet molecular oxygen [O2(1Deltag)]: mechanistic studies using 18O-labeled hydroperoxides, mass spectrometry, and light emission measurements

Proteins have been considered important targets for reactive oxygen species. Indeed, tryptophan (W) has been shown to be a highly susceptible amino acid to many oxidizing agents, including singlet molecular oxygen [O2(1Deltag)]. In this study, two cis- and trans-tryptophan hydroperoxide (WOOH) isomers were completely characterized by HPLC/mass spectrometry and NMR analyses as the major W-oxidation photoproducts. These photoproducts underwent thermal decay into the corresponding alcohols. Additionally, WOOHs were shown to decompose under heating or basification, leading to the formation of N-formylkynurenine (FMK). Using 18O-labeled hydroperoxides (W18O18OH), it was possible to confirm the formation of two oxygen-labeled FMK molecules derived from W18O18OH decomposition. This result demonstrates that both oxygen atoms in FMK are derived from the hydroperoxide group. In addition, these reactions are chemiluminescent (CL), indicating a dioxetane cleavage pathway. This mechanism was confirmed since the CL spectrum of the WOOH decomposition matched the FMK fluorescence spectrum, unequivocally identifying FMK as the emitting species.     

Using sertraline in postpartum and breastfeeding: balancing risks and benefits

Introduction: The World Health Organization recommends newborns to be breastfed but this may be challenging if the mother needs to be treated for depression, since strong evidence to inform treatment choice is missing.

Areas covered: We provide a critical review of the literature to guide clinicians who are considering sertraline for the management of depression during postpartum.

Expert opinion: Sertraline is one of the safest antidepressants during breastfeeding. In most cases, women already taking sertraline should be advised to breastfeed and continue the medication. We recommend to begin with low doses and to slowly increase the dose up, with careful monitoring of the newborn for adverse effects (irritability, poor feeding, or uneasy sleep, especially if the child was born premature or had low weight at birth). The target dose should be the lowest effective. When feasible, child exposure to the medication may be reduced by avoiding breastfeeding at the time when the antidepressant milk concentration is at its peak. A decision to switch to sertraline from ongoing and effective treatment should be taken only after a scrupulous evaluation of the potential risks and benefits of switching versus continuing the ongoing medication while monitoring the infant carefully.     

Vertebral bone density by quantitative computed tomography mirrors bone structure histomorphometric parameters in hemodialysis patients

Diagnosing low bone mass is of clinical importance for hemodialysis (HD) patients due to its association with fractures and cardiovascular disease. We investigated whether bone density obtained by quantitative computed tomography (QCT) is associated with the histologically determined bone volume and microarchitecture parameters in HD patients. Twenty-six HD patients were studied. Bone biopsy samples were obtained from the iliac crest and trabecular bone volume, thickness, number and separation were evaluated by histomorphometry. Vertebral trabecular bone density (VTBD) was evaluated by QCT. VTBD correlated positively with trabecular bone volume (r = 0.69, p < 0.001), trabecular thickness (r = 0.45, p = 0.022) and trabecular number (r = 0.62, p < 0.001), and negatively with trabecular separation (r = ?0.50, p < 0.01). In the multiple linear regression analysis adjusting for age, gender and diabetes, VTBD remained associated with bone volume by histomorphometry (β = 0.06; 95 % CI 0.02–0.11; p = 0.006; R ² = 0.49). VTBD measured by QCT mirrored bone volume and microarchitecture parameters obtained by histomorphometry in HD patients.     

Comprehension of reversible active and passive sentences in agrammatism

Agrammatism is a language disorder characterised by a morphological and/or syntactic deficit in spontaneous speech. Such deficits are usually associated with comprehension disorders - though it is said that this is not always the case - which result in a certain degree of variability in syntactic, lexical, and morpholexical performance. The purpose of this study is to reconsider the nature of comprehension disorders in agrammatism, to test whether Grodzinsky's Trace Deletion Hypothesis (TDH) can be generalised to all agrammatic patients, and to ascertain whether the pattern of impairment observed in agrammatism differs from that present in fluent aphasic patients. Eleven agrammatic patients were tested by means of a sentence comprehension task comprising simple active and passive reversible sentences. The performance of the agrammatic patients was compared to that of 16 fluent aphasic (10 Wernicke's and 6 conduction) and 10 control subjects. The deficits observed in the agrammatic subjects were compatible with the TDH, but there was also impaired processing of pronouns (elements that are also subject to movement) and a mild deficit on the processing of simple active sentences. The fluent aphasic patients showed a similar pattern of impairment. A logistic regression analysis was then applied to each single case separately, in order to study the homogeneity of the patients' performance within each aphasic subgroup. Of the 11 agrammatic patients, 3 did not show comprehension disorders, 5 had a specific deficit for passive movement, 1 a lexical deficit for pronouns only, and 1 a pattern of impairment compatible with Linebarger et al.'s trade-off theory. The last patient showed a deficit for simple active reversible sentences compatible with damage to the mapping of grammatical functions to thematic roles. Similar patterns of impairment were also found in the fluent aphasic sample. Overall, the results lead to the conclusion that the TDH cannot be generalised to all agrammatic patients, that the mechanism it invokes is not the only source responsible for agrammatic comprehension disorders and also contributes to comprehension disorders in fluent aphasic patients.     

Fronto-temporal dementia presenting as Geschwind's syndrome

Geschwind described a syndrome (Geschwind syndrome, GS) in patients with temporal lobe epilepsy, characterized by sexual behavioural disorders, hyper-religiosity, hypergraphia and viscosity. In this report we describe a patient affected by fronto-temporal dementia (FTD), who showed all the personality changes of GS without having epilepsy, and suggest that clinicians should be aware of several other features in FTD, such as hyposexuality and hypergraphia, which are usually not noted during the diagnostic evaluation.     

Atg16L1 deficiency confers protection from uropathogenic Escherichia coli infection in vivo

Urinary tract infection (UTI), a frequent and important disease in humans, is primarily caused by uropathogenic Escherichia coli (UPEC). UPEC forms acute cytoplasmic biofilms within superficial urothelial cells and can persist by establishing membrane-enclosed latent reservoirs to seed recurrent UTI. The host responds with an influx of innate immune cells and shedding of infected epithelial cells. The autophagy gene ATG16L1 has a commonly occurring mutation that is associated with inflammatory disease and intestinal cell abnormalities in mice and humans. Here, we show that Atg16L1-deficient mice (Atg16L1(HM)) cleared bacteriuria more rapidly and thoroughly than controls and showed rapid epithelial recovery. Atg16L1 deficiency was associated with a potent proinflammatory cytokine response with increased recruitment of monocytes and neutrophils to infected bladders. Chimeric and genetic studies showed that Atg16L1(HM) hematopoietic cells alone could increase clearance and that Atg16L1-deficient innate immune cells were required and sufficient for enhanced bacteriuric clearance. We also show that Atg16L1-deficient mice exhibit cell-autonomous architectural aberrations of superficial urothelial cells, including increases in multivesicular bodies, lysosomes, and expression of the UPEC receptor Up1a. Finally, we show that Atg16L1(HM) epithelial cells contained a significantly reduced number of latent reservoirs. Together, our results show that Atg16L1 deficiency confers protection in vivo to the host against both acute and latent UPEC infection, suggest that deficiency in a key autophagy protein can be protective against infection in an animal model of one of the most common diseases of women worldwide, and may have significant clinical implications for understanding the etiology of recurrent UTIs.