Genesis of hepatic fibrosis and its biochemical markers

Liver fibrosis is characterized by an abnormal hepatic accumulation of extracellular matrix (ECM) that results from both increased deposition and reduced degradation of collagen fibres. Fibrotic liver injury results in activation of the hepatic stellate cell (HSC). Surrogate markers are gradually being substituted for biomarkers that reflect the complex balance between synthesis and degradation of the extracellular matrix. Once the hepatic stellate cell is activated, the preceding matrix changes and recurrent injurious stimuli will perpetuate the activated state. The ECM directs cellular differentiation, migration, proliferation and fibrogenic activation or deactivation. The metabolism of the extracellular matrix is closely regulated by matrix metalloproteinases (MMP) and their specific tissue inhibitors (TIMP). Although liver biopsy combined with connective tissue stains has been a mainstay of diagnosis, there is a need for less invasive methods. These diagnostic markers should be considered in combination with liver function tests, ultrasonography and clinical manifestations.     

Minimal access surgery of pediatric inguinal hernias: a review

Inguinal hernia is a common problem among children, and herniotomy has been its standard of care. Laparoscopy, which gained a toehold initially in the management of pediatric inguinal hernia (PIH), has managed to steer world opinion against routine contralateral groin exploration by precise detection of contralateral patencies. Besides detection, its ability to repair simultaneously all forms of inguinal hernias (indirect, direct, combined, recurrent, and incarcerated) together with contralateral patencies has cemented its role as a viable alternative to conventional repair. Numerous minimally invasive techniques for addressing PIH have mushroomed in the past two decades. These techniques vary considerably in their approaches to the internal ring (intraperitoneal, extraperitoneal), use of ports (three, two, one), endoscopic instruments (two, one, or none), sutures (absorbable, nonabsorbable), and techniques of knotting (intracorporeal, extracorporeal). In addition to the surgeons’ experience and the merits/limitations of individual techniques, it is the nature of the defect that should govern the choice of technique. The emerging techniques show a trend toward increasing use of extracorporeal knotting and diminishing use of working ports and endoscopic instruments. These favor wider adoption of minimal access surgery in addressing PIH by surgeons, irrespective of their laparoscopic skills and experience. Growing experience, wider adoption, decreasing complications, and increasing advantages favor emergence of minimal access surgery as the gold standard for the treatment of PIH in the future. This article comprehensively reviews the laparoscopic techniques of addressing PIH.     

Histological characterization and development of mesial surface sulci in the human brain at 13–15 gestational weeks through high-resolution histology

Cellular-level anatomical data from early fetal brain are sparse yet critical to the understanding of neurodevelopmental disorders. We characterize the organization of the human cerebral cortex between 13 and 15 gestational weeks using high-resolution whole-brain histological data sets complimented with multimodal imaging. We observed the heretofore underrecognized, reproducible presence of infolds on the mesial surface of the cerebral hemispheres. Of note at this stage, when most of the cerebrum is occupied by lateral ventricles and the corpus callosum is incompletely developed, we postulate that these mesial infolds represent the primordial stage of cingulate, callosal, and calcarine sulci, features of mesial cortical development. Our observations are based on the multimodal approach and further include histological three-dimensional reconstruction that highlights the importance of the plane of sectioning. We describe the laminar organization of the developing cortical mantle, including these infolds from the marginal to ventricular zone, with Nissl, hematoxylin and eosin, and glial fibrillary acidic protein (GFAP) immunohistochemistry. Despite the absence of major sulci on the dorsal surface, the boundaries among the orbital, frontal, parietal, and occipital cortex were very well demarcated, primarily by the cytoarchitecture differences in the organization of the subplate (SP) and intermediate zone (IZ) in these locations. The parietal region has the thickest cortical plate (CP), SP, and IZ, whereas the orbital region shows the thinnest CP and reveals an extra cell-sparse layer above the bilaminar SP. The subcortical structures show intensely GFAP-immunolabeled soma, absent in the cerebral mantle. Our findings establish a normative neurodevelopment baseline at the early stage.     

Concomitant cervical and lumbar intradural intramedullary lipoma

BACKGROUND: Lipomas of the spinal cord are often a component of spinal dysraphic states. Nondysraphic intramedullary spinal cord lipomas are rare, and concomitant isolated cervical and lumbar intradural intramedullary lipomata are very rare. One patient with concomitant isolated nondysraphic cervical and lumbar spinal cord lipomata has been reported and management options discussed. CASE DESCRIPTION: A young girl presented with insidious-onset diffuse neck pain and early myelopathic signs. Conventional radiographs were normal. Magnetic resonance imaging of the whole neuraxis revealed concomitant cervical and lumbar intradural intramedullary lipoma. Subtotal resection of the lesion was performed at both levels, after which the patient improved symptomatically and was ambulant independently. CONCLUSION: Concomitant intradural lipomas at 2 different locations unassociated with a dysraphic state is very rare. Magnetic resonance imaging with fat suppression study is the investigation of choice. Adequate decompression with subtotal removal is the treatment of choice.     

Antinociceptive and anti-inflammatory effects of Thespesia populnea bark extract

The ethanolic extract of Thespesia populnea bark (TPE) was investigated for anti-inflammatory and analgesic activity at the doses (p.o.) of 100, 200 and 400mg/kg body weight. For evaluation of inflammation carrageenan-, histamine- and serotonin-induced paw edema served as acute models and formaldehyde-induced arthritis served as a chronic model in rats. The acetic acid-induced writhing response and formalin-induced paw licking time in the early and late phases of mice were used to assess analgesic activity. The higher doses of TPE (200 and 400mg/kg, p.o.) were inhibiting carrageenan, histamine and serotonin-induced paw edema as well as formaldehyde-induced arthritis successfully. In addition, TPE (200 and 400mg/kg, p.o.) significantly attenuated the writhing responses induced by an intraperitoneal injection of acetic acid and late phase of pain response induced by an subplantar injection of formalin in mice. Furthermore, our phytochemical studies indicated that the ethanolic extract of bark contains alkaloids, carbohydrates, protein, tannins, phenols, flavonoids, gums and mucilage, saponins and terpenes. From acute oral toxicity studies (OECD-423 guidelines), no mortality was observed even at highest dose of TPE (2000mg/kg, p.o.).     

Suppression of PTEN expression is essential for antiapoptosis and cellular transformation by oncogenic Ras

Ras is one of the most commonly mutated oncogenes in the array of human cancers. The mechanism by which Ras induces cellular transformation is, however, not fully elucidated. We present here evidence that oncogenic Ras suppresses the expression of the tumor suppressor phosphatase and tensin homologue deleted from chromosome 10 (PTEN), and this action of oncogenic Ras is mediated by the Raf-mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK pathway via up-regulation of c-Jun. Jun(+/+) cells undergo cellular transformation by oncogenic Ras, and restoration of wild-type PTEN, but not a phosphate-defective mutant of PTEN, induces apoptosis in these cells. Conversely, in Jun(-/-) cells, oncogenic Ras neither suppresses PTEN nor causes transformation, but rather it induces PTEN-dependent apoptosis. An apoptotic response to oncogenic Ras in Jun(-/-) cells can be prevented by suppressing PTEN expression. These findings imply that oncogenic Ras suppresses the apoptotic gene PTEN via the Raf-MEK-ERK-c-Jun pathway to induce antiapoptosis and cellular transformation. Together, our findings identify a novel molecular interface between the oncogenic and tumor suppressor pathways that regulates cellular transformation and survival.     

Complementary medicine: use and attitudes among GPs

BACKGROUND: Information about use and attitudes of GPs towards complementary medicine is required in order to inform the debate about its place within mainstream medicine. There is evidence that public use of complementary medicine is particularly high in the South-West of England. OBJECTIVE: This study aimed to determine the use of, and attitudes towards, complementary medicine among GPs. METHODS: A questionnaire survey was performed of all primary care physicians working in the health service in Devon and Cornwall. RESULTS: Replies were received from 461 GPs, a response rate of 47%. A total of 314 GPs (68%, range 32-85%) had been involved in complementary medicine in some way during the previous week. One or other form of complementary medicine was practised by 74 of the respondents (16%), the two most common being homoeopathy (5.9%) and acupuncture (4.3%). In addition, 115 of the respondents (25%) had referred at least one patient to a complementary therapist in the previous week, and 253 (55%) had endorsed or recommended treatment with complementary medicine. Chiropractic, acupuncture and osteopathy were rated as the three most effective therapies, and the majority of respondents believed that these three therapies should be funded by the health service. A total of 176 (38%) of respondents reported adverse effects, most commonly after manipulation. CONCLUSION: Over two-thirds of the GPs in Devon and Cornwall who responded to the survey had been involved with complementary medicine in some way during the previous week. This figure is higher than the national average. The majority of respondents believed that acupuncture, chiropractic and osteopathy were effective and should be funded by the NHS.