New optimized piperamide analogues with potent in vivo hypotensive properties

We describe herein the structural optimization of new piperamide analogues, designed from two natural prototypes, piperine 1 and piperdardine 2, obtained from Piper tuberculatum Jacq. (Piperaceae). Molecular modeling studies using semiempirical AM1 method were made in order to establish rational modifications to optimize them by molecular simplification. The targeted compounds (10) and (11) were respectively obtained using benzaldehyde (12) and para-anisaldehyde (13) as starting materials. ¹H NMR spectra showed that the target compounds were diastereoselectively obtained as the (E)-isomer, the same geometry of the natural prototypes. These new synthetic amides presented significant hypotensive effects in cardiovascular essays using in vivo methodologies. Compound 11 (N-[5-(4′-methoxyphenyl)-2(E)-pentenoyl]thiomorpholine) showed a potency 10,000 times greater than its prototype 5, evidencing an optimization of the molecular architecture for this class of hypotensive drug candidates.     

Investigation of Genetic Polymorphisms Related to the Outcome of Radiotherapy for Prostate Cancer Patients

The purpose of this study was to evaluate the association between ATM, TP53 and MDM2 polymorphisms in prostate cancer patients and morbidity after radiotherapy. The presence of ATM (rs1801516), TP53 (rs1042522, rs1800371, rs17878362, rs17883323, and rs35117667), and MDM2 (rs2279744) polymorphisms was assessed by direct sequencing of PCR fragments from 48 patients with histologically proven prostate adenocarcinoma and treated with external beam radiation. The side effects were classified according to the Radiation Therapy Oncology Group (RTOG) score. The results showed no association between clinical characteristics and the development of radiation toxicities (P > 0.05). The C>T transition in the position 16273 (intron 3) of TP53 (rs35117667) was significantly associated with the risk of acute skin toxicity (OR: 0.0072, 95% CI 0.0002–0.227, P = 0.003). The intronic TP53 polymorphism at position 16250 (rs17883323) was associated with chronic urinary toxicity (OR: 0.071, 95%CI 0.006–0.784, P = 0.032). No significant associations were found for the remaining polymorphisms (P > 0.05). The results show that clinical characteristics were not determinant on the developing of radiation sensitivity in prostate cancer patients, and intronic TP53 polymorphisms would be associated with increased acute and chronic radiation toxicities. These observations corroborate the importance of investigating the genetic profile to predict adverse side effects in patients undergoing radiotherapy.     

Are the severe injuries of cutaneous leishmaniasis caused by an exacerbated Th1 response?

American tegumentary leishmaniasis (ATL) is a disease whose clinical features are strongly related to the type of immune response it induces. Herein we report an atypical presentation of cutaneous leishmaniasis in a woman with a severe and extensive sore located in her leg, and we describe the differences between the usual local immune response in ATL and the local immune response in this patient. We observed an intense inflammatory response characterized by Th1 cells and cytokines with conspicuous expression of Toll-like receptor 3 (TLR-3). Few parasites were present, but there was an extensive tissue damage. We also discuss the immunological factors that could be related to the atypical presentation.     

Phenotypic and genotypic characterization of enteroaggregative Escherichia coli isolates from pediatric population in Pakistan

Enteroaggregative Escherichia coli (EAEC) are a leading cause of diarrhea among children. The objective of this study was to define the frequency of EAEC among diarrheal children from flood‐affected areas as well as sporadic cases, determine multidrug resistance, and evaluation of virulence using an in vivo model of pathogenesis. Stool samples were collected from 225 diarrheal children from 2010 to 2011 from flood‐affected areas as well as from sporadic cases in Pakistan. Identified EAEC isolates were characterized by phylogrouping, antibiotic resistance patterns including the extended‐spectrum beta lactamase spectrum, single nucleotide polymorphism detection in gyrA and parC, and virulence potential using wax worm, G. mellonella. A total of 35 (12.5%) confirmed EAEC isolates were identified among 225 E. coli isolates. EAEC isolates displayed high resistance to tetracycline, ampicillin, and cefaclor. A total of 34.28% were ESBL positive. Single nucleotide polymorphism detection revealed 37.14% and 68.57% isolates were positive for SNPs in gyrA (A₆₆₀‐T₆₆₀) and parC (C₃₃₀‐T₃₃₀), respectively. Phylogrouping revealed that B2 phylogroup was more prevalent among all EAEC isolates tested followed by D, A, B1, and non‐typeable (NT). Infection of G. mellonella with EAEC showed that killing infective dose was 100% higher than E. coli DH5 alpha control. EAEC are prevalent among Pakistani children with diarrhea, they are highly resistant to antibiotics, and predominantly fall into B2 phylogroup. Epidemiologic surveillance of EAEC and other E. coli pathotypes is critical to assess not only the role of these pathogens in diarrheal disease but also to determine the extent of multidrug resistance among the population.     

Safety of a physical therapy protocol for women with preeclampsia: a randomized controlled feasibility trial

Objective: To assess the feasibility and safety of a physiotherapy protocol applied to pregnant women with preeclampsia. Methods: Randomized, controlled, single-blind feasibility study, with 24 hospitalized pregnant women with preeclampsia. The intervention group received one session of the physiotherapy. The control group remained under the routine care of the hospital. The primary outcomes were Doppler velocimetry, cardiotocography, and maternal–fetal hemodynamics. Secondary outcomes were pain and anxiety assessed before and after the interventions. A mixed effects linear regression model was used, and the data were compared with the level of significance at 5%. Results: The baseline characteristics of the participants were homogeneous between groups. Resistance index of the Middle Cerebral Artery (MAC) and Umbilical Artery (UA) and cardiotocography did not change significantly. The systolic blood pressure (SBP) increased 4.90 mmHg in the control group and 0.22 mmHg in the intervention group. The diastolic blood pressure (DBP) increased 1.34 mmHg in the control group and decreased 0.40 mmHg in the intervention group. The middle bood pressure (MBP) increased 4.66 mmHg in the control group while there was a decrease of 0.09 mmHg in the intervention group, without statistical difference. Heart rate (HR) decreased 0.94 bpm in the control group; whereas, in the intervention group, there was an increase of 6.30 bpm. The pain reduced clinically 2 points after the intervention. The anxiety reduced clinically in both the groups (?1.26 in the intervention group and ?2.17 in the control group). Conclusion: The protocol applied in the intervention group is feasible and safe for both mother and fetus. Both groups showed clinical reduction in the levels of anxiety; whereas, pain was clinically reduced in the intervention group.     

Recurrent hemi-hypoesthesia in a young patient: A clinical challenge

Takayasu’s arteritis (TA) is a chronic inflammatory disease of unknown etiology characterized by granulomatous vasculitis of medium and large arteries, principally the aorta and its branches. It is a rare disorder but neurological manifestations are common.The authors present a case of a 39-year-old woman that presented with several episodes of hemi-hypoesthesia that lasted several days and coursed with complete recovery. She had already preliminary workup for most neurological diseases that presented at her age range that had been normal.We emphasize in this clinical case the atypical presentation of TA with neurological symptoms of somewhat vague and prolonged course with a negative preliminary workup. We believe it is important to keep a high index of suspicion in such cases.