Hymenaea stigonocarpa Mart. ex Hayne: A tropical medicinal plant with intestinal anti-inflammatory activity in TNBS model of intestinal inflammation in rats

Ethnopharmacological relevance

Stem bark and fruit pulp of Hymenaea stigonocarpa Mart ex. Hayne (Fabaceae) has been popularly used to treat inflammation and gastrointestinal diseases including ulcers, diarrhea and gastric pain. The aim of this study was to investigate the intestinal anti-inflammatory activity of a methanol extract derived from the stem bark and diet with fruit pulp of Hymenaea stigonocarpa in the TNBS model of intestinal inflammation in rats.

Material and methods

The intestinal anti-inflammatory activity of stem bark extract (100, 200 and 400 mg/kg) and fruit pulp (10% and 5% in diet) was measured against the intestinal inflammatory process induced by TNBS (trinitrobenzesulphonic acid) in rats. The protective effects were evaluated as follows: evaluation of intestinal damage (damage score, extension of lesion, colon weight/length ratio), incidence of diarrhea and adherence to adjacent organs, colon glutathione (GSH) and malondialdehyde (MDA) contents, myeloperoxidase (MPO) and alkaline phosphatase (AP) activities. In addition, in vitro studies on lipid peroxidation in rat brain membranes and phytochemical profile were performed with both stem bark and fruit pulp.

Results

Treatment with 100, 200 and 400 mg/kg of stem bark extract and 10% fruit pulp flour showed protective effects in the TNBS-induced colon damage, which was related to inhibition of MPO and AP activities, reduction in colon MDA content, and counteraction of GSH depletion induced by inflammatory process. A concentration-dependent inhibitory effect on the lipid peroxidation in rat brain membranes for stem bark and fruit pulp was determined, with an IC₅₀ value of 5.25±0.23 μg/mL and 27.33±0.09 μg/mL, respectively. Similar phytochemical composition was observed in fruit and stem bark, including mainly flavonoids, condensed tannins and terpenes.

Conclusions

Stem bark extract and fruit pulp flour of Hymenaea stigonocarpa prevented TNBS-induced colonic damage in rats and this protective effect were associated to an improvement of intestinal oxidative stress. The observed anti-inflammatory and antioxidant effects may be associated to the presence of flavonoids and tannins in the stem bark and fruit pulp of Hymenaea stigonocarpa.     

The function,mechanisms, and role of the genes PTEN and TP53 and the effects of asbestos in the development of malignant mesothelioma: a review focused on the genes' molecular mechanisms

The malignant mesothelioma is an aggressive form of cancer with a mean survival rate of less than a year. Moreover, environmental exposure to minerals is an important factor in the development of malignant mesothelioma (MM), especially the mineral asbestos, which has a well-documented role in MM, and more recently, the mineral erionite has been proven to be a strong carcinogenic inducer of MM. In addition, the virus simian virus 40 has been implicated as a co-carcinogenic player in MM. However, the molecular mechanisms involved in the pathogenesis of this cancer are still not fully understood. Indeed, it is known that several genes are altered or mutated in MM, among those are p16^INK4A, p14^ARF, and neurofibromatosis type II. Furthermore, TP53 has been reported to be mutated in the majority of the cancers; however, in MM, it is very uncommon mutations in this gene. Also, the PTEN gene has been shown to play an important role in endometrial cancer and glioblastoma, although the role of PTEN in MM has yet to be established. Taken altogether, this review focuses on the historical aspects, molecular mechanisms, interaction with other genes and proteins, and the role of these genes in MM. Lastly, this review questions the cancer theory of the two hits because the functions of both PTEN and TP53 are not fully explained by this theory.     

Incremental prognostic value of diastolic dysfunction in low risk patients undergoing echocardiography: beyond Framingham score

We sought to assess the prognostic value of diastolic dysfunction (DD) in low-risk adults beyond Framingham risk score (FRS). Consecutive patients without cardiovascular risk factors or co-morbidities were identified from a retrospective cohort. Multivariate binary logistic regression was performed to identify factors associated with DD, and Cox proportional hazard model to evaluate the association of DD with all-cause death. Analysis was repeated by stratifying by the year of the echocardiogram to account for possible time-related shift in measurement techniques. Net reclassification improvement (NRI) was performed to assess incremental prognostic value of DD. The study cohort consisted on 1,039 patients with a mean age (SD) 47.9 (15.7) years. Overall, 346 patients (33.3 %) had DD, among whom 327 were grade 1. Age was the only independent predictor of DD with odds ratio 3.2 (2.8; 3.7) for every 10 years increase (p < 0.0001). After a mean follow-up time (SD) of 7.3 (1.7) years, 71 (6.8 %) patients died. Adjusting for age, gender, and race, DD remained an independent predictor of all-cause mortality with hazard ratio (95 % CI) 2.03 (p = 0.029), and similarly after adjusting for FRS (HR 2.73, p = 0.002) which resulted in IDI gain of 1.4 % (p = 0.0037) and NRI of 15 % (p = 0.029). In 463 age and gender matched subgroups, DD was still an independent predictor of mortality (HR 2.6 [1.25; 5.55], p = 0.01). In low-risk adult outpatients undergoing echocardiography, DD was associated with 2–3 fold increase in risk of death and had incremental prognostic value beyond FRS.     

Human iliac crest cancellous bone elastic modulus and hardness differ with bone formation rate per bone surface but not by existence of prevalent vertebral fracture

The goals of this study were to measure tissue-level elastic moduli and hardness of human cancellous bone using nanoindentation, and determine the relationship between nanoindentation results and previously measured bone histomorphometric variables and bone mineralization. Forty iliac crest biopsies were used in this study, which were collected from Caucasian females with vertebral fracture or from a normal healthy female Caucasian population. They were also categorized into two groups according to high or low bone formation rate per bone surface (BFR/BS). Thirty-two sites were randomly selected on each specimen for nanoindentation with a Berkovich diamond indenter. Two sets of elastic moduli and hardness were calculated using the continuous stiffness measurement method and the Oliver-Pharr method, respectively. Relationships between nanoindentation results and donor age, bone mineralization, and histomorphometric variables were examined. No difference in elastic moduli or hardness was observed between the normal and fracture groups. Significantly lower elastic moduli were observed in the high BFR/BS group. The elastic moduli and hardness measurements were not significantly correlated with the bone mineralization measured independently in a previous study. Linear correlation between elastic modulus and hardness calculated using the Oliver-Pharr method was not different between the normal and fracture groups or between the high and low BFR/BS groups. Nanoindentation hardness was a very good predictor of bone tissue elastic modulus for both normal and osteoporotic bone tissues. Osteoporosis may not change the relationship between bone tissue elastic modulus, bone hardness, and bone mineralization.     

Systematic evaluation of variability in ChIP-chip experiments using predefined DNA targets

The most widely used method for detecting genome-wide protein-DNA interactions is chromatin immunoprecipitation on tiling microarrays, commonly known as ChIP-chip. Here, we conducted the first objective analysis of tiling array platforms, amplification procedures, and signal detection algorithms in a simulated ChIP-chip experiment. Mixtures of human genomic DNA and "spike-ins" comprised of nearly 100 human sequences at various concentrations were hybridized to four tiling array platforms by eight independent groups. Blind to the number of spike-ins, their locations, and the range of concentrations, each group made predictions of the spike-in locations. We found that microarray platform choice is not the primary determinant of overall performance. In fact, variation in performance between labs, protocols, and algorithms within the same array platform was greater than the variation in performance between array platforms. However, each array platform had unique performance characteristics that varied with tiling resolution and the number of replicates, which have implications for cost versus detection power. Long oligonucleotide arrays were slightly more sensitive at detecting very low enrichment. On all platforms, simple sequence repeats and genome redundancy tended to result in false positives. LM-PCR and WGA, the most popular sample amplification techniques, reproduced relative enrichment levels with high fidelity. Performance among signal detection algorithms was heavily dependent on array platform. The spike-in DNA samples and the data presented here provide a stable benchmark against which future ChIP platforms, protocol improvements, and analysis methods can be evaluated.     

Surgical or biologic sphincterotomy in the treatment of chronic anal fissure

BACKGROUND: Chronic anal fissure is a lineal ulcer of the lower part of the anal canal. It is a painful condition characterized by postdefecational pain and bleeding. It is associated with internal anal sphincter spasm. The relief of internal anal sphincter spasm is the key for providing fissure healing. Gold standard in the treatment of chronic anal fissure is partial lateral internal anal sphincterotomy. METHODS: Sixty patients with chronic anal fissure were randomly assigned into two groups treated either by surgical sphincterotomy or injections of botulinum toxin into internal anal sphincter. Manometric measurements were performed before and three months after treatment. Follow up period was six months. The aim of the study was to compare results between these two groups. RESULTS: Both methods efficiently reduced resting anal pressure and successfully healed chronic anal fissure. CONCLUSION: Surgical and biologic sphincterotomy are almost equally effective in the treatment of chronic anal fissure. Injecting botulinum toxin into internal anal sphincter is a safe, easy to apply and effective method in the management of anal fissure.     

Enlarged vestibular aqueduct (EVA) related with recurrent benign paroxysmal positional vertigo (BPPV)

The vestibular aqueduct is a bony canal related to the bony labyrinth of the inner ear and represents the non-sensory components of the endolymph-filled, closed, membranous labyrinth. The association of congenital sensorineural hearing loss with a large or enlarged vestibular aqueduct is well known as the large vestibular aqueduct syndrome (LVAS). The enlarged VA (EVA) comprises abnormalities not only in the structure of the inner ear, but also in the physiology of the auditory and vestibular systems. The clinical picture of this clinical entity is variable [Yetiser S, Kertment M, Ozkaptan Y. Vestibular disturbance in patients with Large Vestibular Aqueduct Syndrome (LVAS). Acta Otolaryngol (StochK) 1999;119: 641-646]. Signs and symptoms of the auditory impairment are more commonly described in the literature: hearing loss ranges from mild to profound, arising from fluctuating to stepwise progressive or sudden. Vestibular disturbances, ranging from mild imbalance to episodic vertigo, are rarely described in the literature. Benign paroxysmal positional vertigo (BPPV) is a labyrinthine disorder with a typical behavior: intense crises of rotational vertigo induced by postural changes of the head, with short duration and usually good responsiveness to rehabilitative maneuvers. These maneuvers are effective in about 80% of patients with BPPV. BPPV often recurs. About 1/3 of patients have a recurrence in the first year after treatment, and by five years, about half of all patients have a recurrence. Vestibular aqueduct has been demonstrated by conventional tomography and computed tomography (CT), however, CT scans cannot show the membranous labyrinth itself. On MR images it is not the vestibular aqueduct that is visualized but its contents, the endolymphatic duct and sac, and can show the abnormalities of the fluid spaces related to the membranous labyrinth. It is proposed that recurrent benign paroxysmal positional vertigo (BPPV) is related with volumetric abnormalities of vestibular aqueduct. This verifiable hypothesis tries to define this rapport and explore new diagnostic and therapeutic possibilities.     

Endophytic population of Pantoea agglomerans in citrus plants and development of a cloning vector for endophytes

Harmless bacteria inhabiting inner plant tissues are termed endophytes. Population fluctuations in the endophytic bacterium Pantoea agglomerans associated with two species of field cultured citrus plants were monitored over a two-year period. The results demonstrated that populations of P. agglomerans fluctuated in Citrus reticulata but not C. sinensis. A cryptic plasmid pPA3.0 (2.9 kb) was identified in 35 out of 44 endophytic isolates of P. agglomerans and was subsequently sequenced. The origins of replication were identified and nine out of 18 open reading frames (ORFs) revealed homology with described proteins. Notably, two ORFs were related to cellular transport systems and plasmid maintenance. Plasmid pPA3.0 was cloned and the gfp gene inserted to generate the pPAGFP vector. The vector was introduced into P. agglomerans isolates and revealed stability was dependent on the isolate genotype, ninety-percent stability values were reached after 60 hours of bacterial cultivation in most evaluated isolates. In order to definitively establish P. agglomerans as an endophyte, the non-transformed bacterium was reintroduced into in vitro cultivated seedlings and the density of inner tissue colonization in inoculated plants was estimated by bacterium re-isolation, while the tissue niches preferred by the bacterium were investigated by scanning electronic microscopy (SEM). Cells from P. agglomerans (strain ARB18) at similar densities were re-isolated from roots, stems and leaves and colonization of parenchyma and xylem tissues were observed. Data suggested that P. agglomerans is a ubiquitous citrus endophyte harboring cryptic plasmids. These characteristics suggest the potential to use the bacterium as a vehicle to introduce new genes in host plants via endophytic bacterial transformation.