Cytopathic effect of Vero cells adapted Bangladeshi strain of peste des petits ruminants (PPR) virus in cell culture.

The present study described the cytopathic effect of PPR virus presently being used in serial passages at the level of 60th in Vero cells and infected tissue culture fluid was used in this study as viral inoculum. Vero cells were grown on cover slip & were infected with tissue culture fluid at a fixed multiplicity of infection (MOI) 0.01. The infected cover slip along with control were stained with H&E stain at periodic intervals and cytopathic effect was studied with microscope. The cytopathic effect (CPE) was visible at first from 24 hpi and the Vero cells showed initial cell rounding, aggregation, and syncytial development. Development of inclusion bodies and cell degradation was noticed by 72 hpi. Complete detachment of the cell monolayer was observed by 84 hpi. It is concluded that, development of numerous inclusion bodies are the indication of well adaptation & extensive multiplication of PPRV in Vero cells.

Clinical manifestations and outcomes of COVID-19 in the paediatric population: a systematic review.

OBJECTIVE: Coronavirus disease 2019 (COVID-19), the respiratory illness caused by severe acute respiratory syndrome coronavirus 2, has affected hundreds of thousands of people. We aim to report the distribution of cases, prevalence, and clinical, radiological, and laboratory signs and outcomes of COVID-19 in paediatric patients. Moreover, we intend to evaluate neonatal clinical outcomes. Hence, our age range of interest is 0 to 19 years. METHODS: A systematic literature review was conducted using the Medline database to identify papers published between 1 December 2019 and 9 April 2020 on COVID-19. RESULTS: The search identified 27 relevant scientific papers and letters. The review showed that the prevalence of COVID-19 in the paediatric population accounts for a small percentage of patients, whose clinical signs and symptoms are often milder than those of adults. Despite better prognosis and low mortality in children, the disease can progress to severe pneumonia in some cases, especially in the presence of co-morbidities. Children are likely to become a hidden source of infection because of their atypical presentation, and they may play a role in community transmission, leading to unfavourable outcomes. There is little evidence about intrauterine vertical transmission. As no vaccine or specific antiviral is currently available, management plans include supportive treatment. CONCLUSION: As compared with that in adults, the presentation of COVID-19 in children is mild and has a better prognosis. Sufficient evidence regarding the probability of intrauterine vertical transmission could not be found, and further studies need to be conducted to establish this relationship.

Incidence, patterns, risk factors, and histopathological findings of liver injury in coronavirus disease 2019 (COVID-19): a scoping review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) exhibits many extrapulmonary manifestations, including liver injury. This scoping review aimed to provide insight into the incidence, patterns, risk factors, histopathological findings, and relationship with disease severity of COVID-19-associated liver injury. Furthermore, we identified existing gaps in the research on the hepatic manifestations of COVID-19 and highlighted areas for future investigations. METHODS: A scoping review was conducted following the methodological framework suggested by Arksey and O'Mallay. Five online databases, along with grey literature, were searched for articles published until 22 May 2020, and we included 62 articles in the review. The research domains, methodological characteristics, and key conclusions were included in the analysis. RESULTS: Retrospective observational studies comprised more than one third (41.9%) of the included publications, and 77.8% were conducted on living patients. The incidence of liver injury varied widely across the studies (4.8%-78%), and liver injury was frequently associated with severe COVID-19. We identified the following risk factors for liver injury: male sex, lymphopoenia, gastrointestinal involvement, old age, increased neutrophil count, and the use of hepatotoxic drugs. Histopathological findings indicate that COVID-19 has direct cytopathic effects and causes liver function test derangements secondary to inflammation, hypoxia, and vascular insult. CONCLUSIONS: Liver injury following COVID-19 infection is common and primarily hepatocellular, with a greater elevation of aspartate aminotransferase tahn of alanine aminotransferase. However, the evidence regarding hepatic failure secondary to COVID-19 is insufficient. Standardised criteria to diagnose liver injury need to be devised. Current use of hepatotoxic drugs necessitates close monitoring of liver function.

Predicting development of ipilimumab-induced hypophysitis: utility of T4 and TSH index but not TSH.

PURPOSE: Ipilimumab, a monoclonal antibody inhibiting CLTA-4, is an established treatment in metastatic melanoma, either alone or in combination with nivolumab, and results in immune mediated adverse events, including endocrinopathy. Hypophysitis is one of the most common endocrine abnormalities. An early recognition of hypophysitis may prevent life threatening consequences of hypopituitarism; therefore, biomarkers to predict which patients will develop hypophysitis would have clinical utility. Recent studies suggested that a decline in TSH may serve as an early marker of IH. This study was aimed at assessing the utility of thyroid function tests in predicting development of hypophysitis. METHODS: A retrospective cohort study was performed for all patients (n = 308) treated with ipilimumab either as a monotherapy or in combination with nivolumab for advanced melanoma at the Royal Marsden Hospital from 2010 to 2016. Thyroid function tests, other pituitary function tests and Pituitary MRIs were used to identify those with hypophysitis. RESULTS AND CONCLUSIONS: Ipilimumab-induced hypophysitis (IH) was diagnosed in 25 patients (8.15%). A decline in TSH was observed in hypophysitis cohort during the first three cycles but it did not reach statistical significance (P = 0.053). A significant fall in FT4 (P < 0.001), TSH index (P < 0.001) and standardised TSH index (P < 0.001) prior to cycles 3 and 4 in hypophysitis cohort was observed. TSH is not useful in predicting development of IH. FT4, TSH index and standardised TSH index may be valuable but a high index of clinical suspicion remains paramount in early detection of hypophysitis.

Evolution of Biomarkers of Atherogenic Risk in Liver Transplantation Recipients.

BACKGROUND: Cardiovascular disease is a major contributing factor to long-term mortality after liver transplantation (LT). METHODS: This study evaluated the evolution of atherogenic risk in liver transplant recipients (LTRs). Thirty-six subjects were prospectively enrolled at 12 months and followed for 48 months after liver transplantation. Serum biomarkers of endothelial dysfunction (sICAM-1 and sVCAM-1), chronic inflammation (serum amyloid A), and oxidative stress (myeloperoxidase) were measured at 12 and 48 months after LT. Additionally, at 12 months all patients underwent a cardiac computed tomography (CT) scan and a coronary artery calcium score (CACS). RESULTS: The prevalence of risk factors of metabolic syndrome (MS) increased over the course of the study. The patients' sVCAM-1 and sICAM-1 increased from 1.82 ± 0.44 ng/mL to 9.10 ± 5.82 ng/mL (P < .001) and 0.23 ± 0.09 ng/mL to 2.7 ± 3.3 ng/mL, respectively from month 12 to 48. Serum myeloperoxidase increased from 0.09 ± 0.07 ng/mL to 3.46 ± 3.92 ng/mL (P < .001) over the course of the study. Serum amyloid A also increased from 21.4 ± 40.7 ng/mL at entry to 91.5 ± 143.6 ng/mL at end of study (P < .001). CONCLUSION: No association between these biomarkers and MS was noted. The cardiac CT revealed mild and moderate disease in 19% and 25% of the cohort, respectively. No association between serum biomarkers and CACS was noted. Serum biomarkers of atherogenic risk increase rapidly in LTRs and precede coronary plaques.

Randomised clinical trial: a leucine-metformin-sildenafil combination (NS-0200) vs placebo in patients with non-alcoholic fatty liver disease.

BACKGROUND: Sirtuin 1 (Sirt1) is suppressed in non-alcoholic fatty liver disease (NAFLD), while its' stimulation or overexpression results in reduced disease severity in pre-clinical NAFLD models. Leucine allosterically activates Sirt1 and synergise with other Sirt/AMPK/NO pathway activators. We developed a triple combination of leucine, metformin and sildenafil (NS-0200), which was effective in a mouse model of non-alcoholic steatohepatitis (NASH). AIM: To report the results from a Phase 2, randomised clinical trial of of NS-0200 in 91 subjects with NAFLD (liver fat ≥15% by magnetic resonance imaging-proton-density fat fraction (MRI-PDFF)). METHODS: Subjects were randomised to placebo, low-dose (1.1 g leucine/0.5 g metformin/0.5 mg sildenafil) or high-dose NS-0200 (1.1 g leucine/0.5 g metformin/1.0 mg sildenafil) b.d. for 16 weeks; change in hepatic fat was assessed via MRI-PDFF, and lipid metabolism was assessed via changes in the lipidomic signature. Seventy subjects completed the trial and met a priori compliance criteria. Analyses were conducted on the full cohort and on those with alanine aminotransferase (ALT) values above median (50 U/L; n = 35). RESULTS: In the full cohort, active treatments did not separate from placebo. High dose NS-0200 reduced hepatic fat by 15.7% (relative change from baseline) in the high ALT group (P < 0.005) while low dose NS-0200 and placebo did not significantly change hepatic fat. Lipidomic analysis showed dose-responsive treatment effects in both overall and high ALT cohorts, with significant decreases in metabolically active lipids and up-regulation of fatty acid oxidation. CONCLUSION: These data support further evaluation of high-dose NS-0200 for treating NASH, especially in those with elevated ALT (NCT 02546609).

Protective effect of black relative to white race against non-alcoholic fatty liver disease in patients with severe obesity, independent of type 2 diabetes.

Severe obesity (body mass index ⩾35 kg m-2) and type 2 diabetes (T2D) are potent and additive risk factors for non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH). Scant available evidence indicates that black relative to white patients with severe obesity are less susceptible to NAFLD, but it is unclear if T2D abolishes this apparent racial disparity. Therefore, we compared biopsy-proven NAFLD and its progression between black (n=71) and white (n=155) patients with severe obesity stratified by presence or absence of T2D. Although prevalence of T2D was similar between races (37%, P>0.9), whites were significantly more likely than blacks to have NAFLD, NASH and advanced fibrosis (defined as bridging fibrosis and/or cirrhosis). Importantly, T2D was associated with increased odds of NAFLD, NASH and advanced fibrosis (defined as bridging fibrosis or cirrhosis) in whites only (P<0.05). In turn, a higher proportion of blacks than whites with T2D were free of NAFLD (58 versus 22%, P<0.01). These preliminary findings question translation of the powerful interconnection between T2D and NAFLD in whites with severe obesity to blacks and point to an important role of race in the pathophysiology and treatment of these diseases.

Technical Note: Evaluation of the systematic accuracy of a frameless, multiple image modality guided, linear accelerator based stereotactic radiosurgery system.

PURPOSE: To evaluate the total systematic accuracy of a frameless, image guided stereotactic radiosurgery system. METHODS: The localization accuracy and intermodality difference was determined by delivering radiation to an end-to-end prototype phantom, in which the targets were localized using optical surface monitoring system (OSMS), electromagnetic beacon-based tracking (Calypso®), cone-beam CT, "snap-shot" planar x-ray imaging, and a robotic couch. Six IMRT plans with jaw tracking and a flattening filter free beam were used to study the dosimetric accuracy for intracranial and spinal stereotactic radiosurgery treatment. RESULTS: End-to-end localization accuracy of the system evaluated with the end-to-end phantom was 0.5 ± 0.2 mm with a maximum deviation of 0.9 mm over 90 measurements (including jaw, MLC, and cone measurements for both auto and manual fusion) for single isocenter, single target treatment, 0.6 ± 0.4 mm for multitarget treatment with shared isocenter. Residual setup errors were within 0.1 mm for OSMS, and 0.3 mm for Calypso. Dosimetric evaluation based on absolute film dosimetry showed greater than 90% pass rate for all cases using a gamma criteria of 3%/1 mm. CONCLUSIONS: The authors' experience demonstrates that the localization accuracy of the frameless image-guided system is comparable to robotic or invasive frame based radiosurgery systems.

Randomised clinical trial: Lactobacillus GG modulates gut microbiome, metabolome and endotoxemia in patients with cirrhosis.

BACKGROUND: Safety of individual probiotic strains approved under Investigational New Drug (IND) policies in cirrhosis with minimal hepatic encephalopathy (MHE) is not clear. AIM: The primary aim of this phase I study was to evaluate the safety, tolerability of probiotic Lactobacillus GG (LGG) compared to placebo, while secondary ones were to explore its mechanism of action using cognitive, microbiome, metabolome and endotoxin analysis in MHE patients. METHODS: Cirrhotic patients with MHE patients were randomised 1:1 into LGG or placebo BID after being prescribed a standard diet and multi-vitamin regimen and were followed up for 8 weeks. Serum, urine and stool samples were collected at baseline and study end. Safety was assessed at Weeks 4 and 8. Endotoxin and systemic inflammation, microbiome using multi-tagged pyrosequencing, serum/urine metabolome were analysed between groups using correlation networks. RESULTS: Thirty MHE patients (14 LGG and 16 placebo) completed the study without any differences in serious adverse events. However, self-limited diarrhoea was more frequent in LGG patients. A standard diet was maintained and LGG batches were comparable throughout. Only in the LGG-randomised group, endotoxemia and TNF-α decreased, microbiome changed (reduced Enterobacteriaceae and increased Clostridiales Incertae Sedis XIV and Lachnospiraceae relative abundance) with changes in metabolite/microbiome correlations pertaining to amino acid, vitamin and secondary BA metabolism. No change in cognition was found. CONCLUSIONS: In this phase I study, Lactobacillus GG is safe and well-tolerated in cirrhosis and is associated with a reduction in endotoxemia and dysbiosis.

Pseudohyperplastic prostate adenocarcinoma with signet ring cells mimicking hyperplastic colonic polyp and associated high grade foamy gland carcinoma. A case report.

Prostatic adenocarcinoma which closely mimics benign prostatic hyperplasia is adenocarcinoma with pseudohyperplastic pattern. The morphological similarities include large glands with papillary infoldings and branching. However the distinguishing features are crowded glands, nuclear enlargement, occasional to frequent nucleoli and abundant pink intraluminal secretions and crystals. There can be large glands with straight luminal borders. These tumors are not only difficult to diagnose but they are also difficult to grade as Gleason scoring system does not account for this histologic pattern. Some of these tumors have shown extraprostatic extension and it has been recommended that pseudohyperplastic adenocarcinoma should not be regarded as a low grade cancer. This is a case report of prostatic adenocarcinoma with pseudohyperplastic pattern and signet ring cells in the glandular epithelium mimicking colonic hyperplastic polyp. In addition there is an associated pattern of high grade foamy gland carcinoma and occasional signet ring cells in the stroma. This combination has not been described in previous studies.

Clinical outcomes of adjuvant chemotherapy and vaginal brachytherapy with or without pelvic radiation for surgical stage I-II uterine serous carcinoma.

OBJECTIVE(S): To evaluate the benefit of adding pelvic radiation treatment (EBRT) to vaginal cuff brachytherapy (VB) for women with early stage uterine serous carcinoma (USC) treated with adjuvant chemotherapy. MATERIALS AND METHODS: After institutional review board (IRB) approval, the authors retrospectively identified 56 patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) Stage I-II USC treated with hysterectomy, bilateral oophorectomy +/- lymphadenectomy, adjuvant chemotherapy, and radiation therapy with either VB alone (n = 33) or VB + EBRT (n = 23) between July 1998 and August 2009. RESULTS: Median age and follow-up were 68.5 years and 54 months respectively. Median VB alone surface dose was 37.5 Gy and median pelvic EBRT dose was 45 Gy. The prevalence of lower uterine segment involvement, > 50% myometrial invasion, and Stage II disease were higher for patients receiving VB + EBRT. Overall, only one vaginal recurrence was observed. Pelvic recurrence rate was 26% for VB + EBRT compared to 12% for VB alone (p = 0.179). The five-year recurrence-free survival (RFS) was 80.5% for VB vs 67.3% for VB + EBRT (p = 0.3847), and the five-year overall survival (OS) was 65.9% for VB vs 66.7% for VB + EBRT (p = 0.7159). On univariate and multivariate analysis, radiation treatment modality was not a predictor for local control or survival. CONCLUSIONS: In this cohort, there was no significant clinical benefit of adding pelvic EBRT to the adjuvant management of early stage uterine serous carcinoma. The higher prevalence of high-risk features in the VB + EBRT group may underestimate the value of this treatment. Further investigation is warranted to identify the optimal radiation treatment regiment for early stage USC treated with surgery and adjuvant chemotherapy.

Rutin prevents cognitive impairments by ameliorating oxidative stress and neuroinflammation in rat model of sporadic dementia of Alzheimer type.

The objective of the present study was to assess the neuroprotective role of rutin (vitamin P) and delineate the mechanism of action. Recent evidence indicates that rutin exhibits antioxidant potential and protects the brain against various oxidative stressors. More precisely, the aim of the present study was to examine the modulating impacts of rutin against cognitive deficits and oxidative damage in intracerebroventricular-streptozotocin (ICV-STZ)-infused rats. Rats were injected bilaterally with ICV-STZ (3 mg/kg), whereas sham rats received the same volume of vehicle. After 2 weeks of streptozotocin (STZ) infusion, rats were tested for cognitive performance using Morris water maze tasks and thereafter euthanized for further biochemical, histopathological, and immunohistochemical studies. Rutin pretreatment (25 mg/kg, orally, once daily for 3 weeks) significantly attenuated thiobarbituric acid reactive substances (TBARS), activity of poly ADP-ribosyl polymerase, and nitrite level and decreased level of reduced glutathione (GSH) and activities of its dependent enzymes (glutathione peroxidase [GPx] and glutathione reductase [GR]) and catalase in the hippocampus of ICV-STZ rats. ICV-STZ rats showed significant cognitive deficits, which was improved significantly by rutin supplementation. The results indicate that rutin attenuates STZ-induced inflammation by reducing the expression of cyclooxygenase-2 (COX-2), glial fibrillary acidic protein (GFAP), interleukin-8 (IL-8), inducible nitric oxide synthase (iNOS), nuclear factor-kB, and preventing the morphological changes in hippocampus. The study thereby suggests the effectiveness of rutin in preventing cognitive deficits and might be beneficial for the treatment of sporadic dementia of Alzheimer type (SDAT).

Design, synthesis and evaluation of unique 2,4,5-triaryl imidazole derivatives as novel potent aspartic protease inhibitors.

The 2,4,5-triaryl imidazole derivatives (API) were designed, screened and characterized kinetically & thermodynamically against Pepsin and their activity was also tested on the in silico platform. The docking studies of API with Pepsin show that these are novel and unique inhibitors of Aspartic protease. Drug like properties of these compounds were validated in silico based on Lipinski's rule of Five by calculating ClogP, LogS, H-bond acceptors, H-Bond donors, rotational bonds, PSA, PB and BBB values. The Et/Ki and Et/Km values of API show that they follow the Michaelis-Menten kinetics. The binding of inhibitors with proteases was explained by using Van't Hoff plot and thermodynamic parameters viz. free energy (ΔG), Entropy (ΔS) and Enthalpy (ΔH). The Van't Hoff analysis showed that the value of Ki decreases with increase in temperature and the binding of the inhibitor are entropically driven. API act as new potent aspartic protease inhibitors with Ki, for Pepsin, ranges from 3.7 µM to 16.7 µM. Strong hydrophobic groups at C-4 & C-5 position in API favor binding of inhibitors with Pepsin. Experiments also showed that among C-2 aryl substituted imidazole, a 4-substitution on aryl ring is preferred and less polar substituent makes the molecule more active whereas polar substituents at 2-position on C-2 aryl ring makes the molecule less active. The docking studies of API with Pepsin further intensify and validate our results.

D-Limonene modulates inflammation, oxidative stress and Ras-ERK pathway to inhibit murine skin tumorigenesis.

D-Limonene, a common monoterepene has been shown to have antiproliferative, apoptosis-inducing and chemopreventive effects. In the present study, we have investigated the effects of D-limonene on the growth of 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor development. We found that D-limonene (50 and 100 mg/kg body weight) treatments to the mouse skin significantly reduced the TPA-induced (a) edema and hyperplasia (p < 0.001); (b) expression of cyclooxygenase-2; (c) ornithine decarboxylase activity (p < 0.001); and (d) [(3)H] thymidine incorporation into DNA (p < 0.001). In addition, treatment of D-limonene effectively restored the level of reduced glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, catalase and malondialdehyde production in TPA-treated mouse skin. In a two-stage skin tumorigenesis study, D-limonene significantly reduced the tumor burden (p < 0.005) and tumor incidence as compared to DMBA/TPA-treated mice. D-Limonene treatment also extended the latency period of tumor development from 4 to 9 weeks. D-Limonene treatment decreased the expression level of Ras, Raf and phosphorylation of extracellular signal-regulated protein kinase 1/2 in DMBA/TPA-induced tumors. A decrease in the expression of Bcl-2 and an increase in Bax expression were also observed in tumor tissues of mice treated with D-limonene. Taken together, our findings suggest that D-limonene may exert its chemopreventive activity through the inhibition of inflammation, oxidative stress and Ras-signaling as well as the induction of pro-apoptotic state during TPA-mediated promotion of DMBA-induced skin cancer in mouse model.

Study of vascular supply of lunate and consideration applied to Kienböck disease.

The purpose of this study was to assess vascularity of the lunate by number of foramina and radiography of vessels of the wrist. The genesis of lunatomalacia requires some vascular risk and mechanical predisposition. The findings were correlated with the cause of Kienböck's disease. The vascular foramina were more than two in 91.33% of the lunate. The lunate had consistent dorsal and palmar branches from radial artery. The additional branches from anterior interosseous artery in 72.22% and a branch of palmar inter carpal arch in 69.44% cases contributed in arterial anastomosis on palmar aspect of lunate. The dorsal blood supply was found by anterior interosseous artery in 85.71% of specimens and dorsal branch from dorsal intercarpal arch in 50% of specimens. The blood supply of lunate comes along with various ligaments which may be disrupted due to trauma or strain leading to avascular necrosis. The present observations are suggestive of rich blood supply of lunate in comparison of other investigations. Therefore Kienböck's disease is less common in northern India.

Mechanism of Wound-Healing Activity of Hippophae rhamnoides L. Leaf Extract in Experimental Burns.

The present investigation was undertaken to evaluate the healing efficacy of lyophilized aqueous leaf extract of Sea buckthorn (Hippophae rhamnoides L., family Elaeagnaceae) (SBT) and to explore its possible mechanism of action on experimental burn wounds in rats. The SBT extract, at various concentrations, was applied topically, twice daily for 7 days. Treatment with silver sulfadiazine (SSD) ointment was used as reference control. The most effective concentration of the extract was found to be 5.0% (w/w) for burn wound healing and this was further used for detailed study. The SBT-treated group showed faster reduction in wound area in comparison with control and SSD-treated groups. The topical application of SBT increased collagen synthesis and stabilization at the wound site, as evidenced by increase in hydroxyproline, hexosamine levels and up-regulated expression of collagen type-III. The histological examinations and matrix metalloproteinases (MMP-2 and -9) expression also confirmed the healing efficacy of SBT leaf extract. Furthermore, there was significant increase in levels of endogenous enzymatic and non-enzymatic antioxidants and decrease in lipid peroxide levels in SBT-treated burn wound granulation tissue. The SBT also promoted angiogenesis as evidenced by an in vitro chick chorioallantoic membrane model and in vivo up-regulated vascular endothelial growth factor (VEGF) expression. The SBT leaf extract had no cytotoxic effect on BHK-21 cell line. In conclusion, SBT aqueous leaf extract possesses significant healing potential in burn wounds and has a positive influence on the different phases of wound repair.

Safety and healing efficacy of Sea buckthorn (Hippophae rhamnoides L.) seed oil on burn wounds in rats.

The present investigation was undertaken to determine the safety and efficacy of supercritical CO2-extracted Hippophae rhamnoides L. (Sea buckthorn) (SBT) seed oil on burn wound model. SBT seed oil was co-administered by two routes at a dose of 2.5 ml/kg body weight (p.o.) and 200 microl (topical) for 7 days on experimental burn wounds in rats. The SBT seed oil augmented the wound healing process as indicated by significant increase in wound contraction, hydroxyproline, hexosamine, DNA and total protein contents in comparison to control and reference control treated with silver sulfadiazine (SS) ointment. Histopathological findings further confirmed the healing potential of SBT seed oil. SBT seed oil treatment up-regulated the expression of matrix metalloproteinases (MMP-2 and 9), collagen type-III and VEGF in granulation tissue. It was observed that SBT seed oil also possesses antioxidant properties as evidenced by significant increase in reduced glutathione (GSH) level and reduced production of reactive oxygen species (ROS) in wound granulation tissue. In acute and sub-acute oral toxicity studies, no adverse effects were observed in any of the groups administered with SBT seed oil. These results suggest that the supercritical CO2-extracted Sea buckthorn seed oil possesses significant wound healing activity and have no associated toxicity or side effects.

Brain penetration effects of microelectrodes and DBS leads in STN or GPi.

OBJECTIVE: To determine how intraoperative microelectrode recordings (MER) and intraoperative lead placement acutely influence tremor, rigidity, and bradykinesia. Secondarily, to evaluate whether the longevity of the MER and lead placement effects were influenced by target location (subthalamic nucleus (STN) or globus pallidus interna (GPi)). BACKGROUND: Currently most groups who perform deep brain stimulation (DBS) for Parkinson disease (PD) use MER, as well as macrostimulation (test stimulation), to refine DBS lead position. Following MER and/or test stimulation, however, there may be a resultant "collision/implantation" or "microlesion" effect, thought to result from disruption of cells and/or fibres within the penetrated region. These effects have not been carefully quantified. METHODS: 47 consecutive patients with PD undergoing unilateral DBS for PD (STN or GPi DBS) were evaluated. Motor function was measured at six time points with a modified motor Unified Parkinson Disease Rating Scale (UPDRS): (1) preoperatively, (2) immediately after MER, (3) immediately after lead implantation/collision, (4) 4 months following surgery-off medications, on DBS (12 h medication washout), (5) 6 months postoperatively-off medication and off DBS (12 h washout) and (6) 6 months-on medication and off DBS (12 h washout). RESULTS: Significant improvements in motor scores (p<0.05) (tremor, rigidity, bradykinesia) were observed as a result of MER and lead placement. The improvements were similar in magnitude to what was observed at 4 and 6 months post-DBS following programming and medication optimisation. When washed out (medications and DBS) for 12 h, UPDRS motor scores were still improved compared with preoperative testing. There was a larger improvement in STN compared with GPi following MER (p<0.05) and a trend for significance following lead placement (p<0.08) but long term outcome was similar. CONCLUSION: This study demonstrated significant acute intraoperative penetration effects resulting from MER and lead placement/collision in PD. Clinicians rating patients in the operating suite should be aware of these effects, and should consider pre- and post-lead placement rating scales prior to activating DBS. The collision/implantation effects were greater intraoperatively with STN compared with GPi, and with greater disease duration there was a larger effect.

Perillyl alcohol attenuates Ras-ERK signaling to inhibit murine skin inflammation and tumorigenesis.

In the present study, the chemopreventive effect of topical application of perillyl alcohol (POH) on 9,10-dimethylbenz(a)anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumorigenesis and its possible mechanisms of action in Swiss albino mice were investigated. We evaluated the effect of pretreatment of POH (6 and 12 mg/kg body weight) on TPA (2 microg/200 microl of acetone)-induced skin edema, hyperplasia, peroxidase damage and modulation in activities of catalase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione contents. Application of POH 30 min prior to TPA treatment, showed a protective effect in almost all the investigated parameters. Additionally, pretreatment with POH showed a significant inhibition of ornithine decarboxylase (ODC) activity and [(3)H] thymidine incorporation into epidermal DNA. In promotion phase, a significant reduction was found in tumor incidence and tumor burden in mice pretreated with POH (12 mg/kg body weight) with extension of the latency period from 4 to 8 weeks as compared to those treated with TPA alone. POH significantly suppressed the Ras/Raf/ERK pathway and induced apoptosis in Swiss albino mice skin. Our findings suggested that the chemopreventive efficacy of POH is probably due to the inhibition of oxidative stress responses, inhibition of the Ras cell proliferation pathway and induction of apoptosis in murine skin tumor promotion phase.