Distribution of 226Ra body burden of workers in an underground uranium mine in India.

Uranium mine workers are exposed to ore dust containing uranium and its daughter products during different mining operations. These radionuclides may pose inhalation hazards to workers during the course of their occupation. The most significant among these radionuclides is (226)Ra. The measurement of radium body burden of uranium mine workers is important to assess their internal exposure. For this purpose, the radon-in-breath measurement technique has been used in the present paper. Workers at the Jaduguda mine, India, associated with different categories of mining operations were monitored between 2001 and 2007. The measurement results indicate that workers--depending on mining operation category--show (226)Ra body burdens ranging from 0.15 to 2.85 kBq. The maximum body burden was found for workers associated with timbering operations, with an average (226)Ra body burden of 0.85 ± 0.54 kBq. Overall, the average value observed for 800 workers was 0.76 ± 0.51 kBq, which gives rise to an average effective dose of 1.67 mSv per year for inhalation and 0.21 mSv per year for ingestion.

Technical skills simulation in transplant surgery: a systematic review.

Purpose:  Transplant surgery is a demanding field in which the technical skills of the surgeon correlates with patient outcomes. As such, there is potential for simulation-based training to play an important role in technical skill acquisition. This study provides a systematic assessment of the current literature regarding the use of simulation to improve surgeon technical skills in transplantation. Methods:  Data were collected by performing an electronic search of the PubMed and Scopus database for articles describing simulation in transplant surgery. The abstracts were screened using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Three reviewers analyzed 172 abstracts and agreed upon articles that met the inclusion criteria for the systematic review. Results:  Simulators can be categorized into virtual reality simulators, cadaveric models, animal models (animate or inanimate) and synthetic physical models. No virtual reality simulators in transplant surgery are described in the literature. Three cadaveric models, seven animal models and eight synthetic physical models specific to transplant surgery are described. A total of 18 publications focusing on technical skills simulation in kidney, liver, lung, pancreas, and cardiac transplantation were found with the majority focusing on kidney transplantation. Conclusions:  This systematic review identifies currently reported simulation models in transplant surgery. This will serve as a reference for general surgery and transplant surgery professionals interested in using simulation to enhance their technical skills.

An in vitro study of Ocimum sanctum as a chemotherapeutic agent on oral cancer cell-line.

Oral squamous cell carcinoma (OSCC) is the most commom cancer in the world. If remain untreated for several years, it may be fatal. Hence, it is important to prevent and treat OSCC at an early stage. In this study the effect of aqueous and dry leaves extract of Ocimum sanctum was observed on Ca9-22 cell line, which is an OSCC cell line. For this, Ca9-22 cell line was cultured and maintained. After 24 h, the cells were treated with aqueous and dry leaves extract of Ocimum sanctum plant. Viability of the cancerous cells were studied by 3-(4, 5-dimethythiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and neutral red uptake (NRU) assay. Minimum inhibitory concentrations (MIC), lethal concentration25 (LC25), lethal concentration50 (LC50) and highest permissive concentration (HPC) was calculated by probit computational method. Experimentally, the MIC value was 5 mg/L, whereas the HPC was 30 mg/L of the plant extract in aqueous state. For the dry extract the MIC was 5 mg/L whereas the HPC was 35 mg/L for both MTT and NRU assays. For MTT assay LC values: 7.41 (LC25), 14.79 (LC50) and 26.91 mg/L (LC75) for aqueous extract and 12.58 (LC25), 20.89 (LC50), 29.51 mg/L (LC75) for dry extract. For NRU assay LC values were 10.23 (LC25), 14.79 (LC50) and 20.89 mg/L (LC75) aqueous extract, and 16.59 (LC25), 23.44 (LC50), 30.19 mg/L (LC75) dry extract of the plant. From the above study it was concluded that, Ocimum sanctum have anti-cancerous activity. It can further be used for therapeutic purposes.

Antibodies to dynorphin a (1-17) attenuate closed head injury induced blood-brain barrier disruption, brain edema formation and brain pathology in the rat.

The potential neuroprotective efficacy of dynorphin A antiserum on BBB dysfunction, edema formation and brain pathology was examined in a closed head injury (CHI) model in the rat. The CHI was produced by an impact of 0.224 N on the right parietal bone under anesthesia by dropping a weight of 114.6 g on the skull from a height of 20 cm through a guide tube. This concussive brain injury resulted in profound BBB disruption as evidenced by leakage of Evans blue and radioiodine in the brain. Edema formation and swelling at 5 h were most pronounced in the contralateral cerebral hemisphere. Pretreatment with dynorphin A antiserum (1:20, monoclonal) infused into the left lateral cerebral ventricle (30 microL in PBS) either 30 min before or 30 min after CHI significantly attenuated BBB dysfunction, brain edema formation, volume swelling and brain pathology. However, no reduction in brain edema, BBB permeability or improved brain pathology was seen when the antiserum was given 60 min post-CHI. These observations are the first to suggest that antiserum to dynorphin when administered into the CSF during early phase of CHI is neuroprotective. Our work further indicates that dynorphin is actively involved in the cellular and molecular mechanisms of edema formation and BBB breakdown in CHI.

Nanowired-drug delivery enhances neuroprotective efficacy of compounds and reduces spinal cord edema formation and improves functional outcome following spinal cord injury in the rat.

The possibility that drugs attached to nanowires enhance their therapeutic efficacy was examined in a rat model of spinal cord injury (SCI). Three Acure compounds AP-173, AP-713 and AP-364 were tagged with TiO(2)-based nanowires (50-60 nm) and applied over the traumatized cord either 5 or 60 min after SCI in rats produced by a longitudinal incision into the right dorsal horn of the T10-11 segments under equithesin anaesthesia. Normal compounds were used for comparison. After 5 h SCI, behavioral outcome, blood-spinal cord barrier (BSCB) permeability, edema formation and cell injury were examined. Topical application of nanowired compound AP-713 (10 microg in 20 microL) when applied either 5 or 60 min after injury markedly attenuated behavioral dysfunction at 2-3 h after SCI and reduces BSCB disruption, edema formation and cord pathology at 5 h compared to other compounds. Whereas normal compounds applied at 5 min after injury (but not after 60 min) had some significant but less beneficial effects compared to their nanowired combinations. On the other hand, nanowires alone did not influence spinal cord pathology or motor function after SCI. Taken together, our results indicate that the nanowired-drug-delivery enhances the neuroprotective efficacy of drugs in SCI and reduces functional outcome compared to normal compounds even applied at a later stage following trauma, not reported earlier.

Acute pancreatic injury induced by COVID-19.

We report a patient with COVID-19 infection presenting with acute pancreatitis. The diagnosis of pancreatitis was based on laboratory as well as radiological evidence, and all the usual etiologies were ruled out. The temporal association with COVID-19 is strongly suggestive of novel coronavirus induced pancreatic injury.

Antibodies to serotonin attenuate closed head injury induced blood brain barrier disruption and brain pathology.

Closed head injury (CHI) often results in profound brain swelling and instant death of the victims due to compression of the vital centers. However, the neurochemical basis of edema formation in CHI is still obscure. Previous studies from our laboratory show that blockade of serotonin synthesis prior to CHI in a rat model attenuates brain edema, indicating a prominent role for serotonin in head injury. Thus, neutralization of endogenous serotonin activity and/or blocking of its receptors will induce neuroprotection in CHI. Since serotonin has more than 14 receptors and selective serotonin antagonists are still not available, we used serotonin antiserum to neutralize its in vivo effects before or after CHI in a rat model. CHI was produced by an impact of 0.224 N on the right parietal skull bone under Equithesin anesthesia by dropping a weight of 114.6 g from a height of 20 cm through a guide tube. This concussive brain injury resulted in blood-brain barrier (BBB) disruption, brain edema formation, and volume swelling at 5 h that were most pronounced in the contralateral cerebral hemisphere. The plasma and brain serotonin levels were increased several-fold at this time. Intracerebroventricular administration of serotonin antiserum (1:20, monoclonal) into the left lateral cerebral ventricle (30 microL in PBS) 30 min before or 30 min (but not 60 min) after CHI significantly attenuated BBB disruption, brain edema formation, volume swelling, and brain pathology. The plasma and brain serotonin levels continued to remain high. These observations are the first to suggest that antiserum to serotonin when administered into the CSF during the early phase of CHI are capable of inducing neuroprotection.

Drug delivery to the spinal cord tagged with nanowire enhances neuroprotective efficacy and functional recovery following trauma to the rat spinal cord.

The possibility that drugs attached to innocuous nanowires enhance their delivery within the central nervous system (CNS) and thereby increase their therapeutic efficacy was examined in a rat model of spinal cord injury (SCI). Three compounds--AP173 (SCI-1), AP713 (SCI-2), and AP364 (SCI-5) (Acure Pharma, Uppsala, Sweden)--were tagged with TiO(2)-based nanowires using standard procedure. Normal compounds were used for comparison. SCI was produced by making a longitudinal incision into the right dorsal horn of the T10-T11 segments under Equithesin anesthesia. The compounds, either alone or tagged with nanowires, were applied topically within 5 to 10 min after SCI. In these rats, behavioral outcome, blood-spinal cord barrier (BSCB) permeability, edema formation, and cell injury were examined at 5 h after injury. Topical application of normal compounds in high quantity (10 microg in 20 microL) attenuated behavioral dysfunction (3 h after trauma), edema formation, and cell injury, as well as reducing BSCB permeability to Evans blue albumin and (131)I. These beneficial effects are most pronounced with AP713 (SCI-2) treatment. Interestingly, when these compounds were administered in identical conditions after tagging with nanowires, their beneficial effects on functional recovery and spinal cord pathology were further enhanced. However, topical administration of nanowires alone did not influence trauma-induced spinal cord pathology or motor functions. Taken together, our results, probably for the first time, indicate that drug delivery and therapeutic efficacy are enhanced when the compounds are administered with nanowires.

Histamine receptors influence blood-spinal cord barrier permeability, edema formation, and spinal cord blood flow following trauma to the rat spinal cord.

The role of histamine in edema formation, blood-spinal cord barrier (BSCB) permeability, and spinal cord blood flow (SCBF) following spinal cord injury (SCI) was examined using modulation of histamine H1, H2, and H3 receptors in the rat. Focal trauma to the spinal cord at the T10-11 level significantly increased spinal cord edema formation, BSCB permeability to protein tracers and SCBF reduction in the T9 and T12 segments. Pretreatment with histamine H1 receptor antagonist mepyramine (1 mg, 5 mg, and 10 mg/kg, i.p.) did not attenuate spinal pathophysiology following SCI. Blockade of histamine H2 receptors with cimetidine or ranitidine (1 mg, 5 mg, or 10 mg/kg 30 minutes before injury) significantly reduced early pathophysiological events in a dose dependent manner. The effects of ranitidine were far superior to cimetidine in identical doses. Pretreatment with a histamine H3 receptor agonist alpha-methylhistamine (1 mg and 2 mg/kg/i.p.), that inhibits histamine synthesis and release in the CNS, thwarted edema formation, BSCB breakdown, and SCBF disturbances after SCI. The lowest dose of histamine H3 agonist was most effective. Blockade of histamine H3 receptors with thioperamide (1 mg, 5 mg/kg, i.p.) exacerbated spinal cord pathology. These observations suggest that stimulation of histamine H3 receptors and blockade of histamine H2 receptors is neuroprotective in SCI.

Zinc protoporphyrin IX attenuates closed head injury-induced edema formation, blood-brain barrier disruption, and serotonin levels in the rat.

The role of heme oxygenase (HO) in closed head injury (CHI) was examined using a potent HO and guanylyl cyclase inhibitor, zinc protoporphyrin (Zn-PP) in the rat. Blood-brain barrier (BBB) permeability to Evans blue and radioiodine, edema formation, and plasma and brain levels of serotonin were measured in control, CHI, and Zn-PP-treated CHI rats. CHI was produced by an impact of 0.224 N on the right parietal bone by dropping 114.6 g weight from a height of 20 cm in anesthetized rats. This concussive injury resulted in edema formation and brain swelling 5 hours after insult that was most pronounced in the contralateral hemisphere. The whole brain was edematous and remained in a semi-fluid state. Microvascular permeability disturbances to protein tracers were prominent in both cerebral hemispheres and the underlying cerebral structures. Plasma and brain serotonin showed pronounced increases and correlated with edema formation. Pretreatment with Zn-PP (10 mg/ kg, i.p) 30 minutes before or after CHI attenuated edema formation, brain swelling, plasma and brain serotonin levels, and microvascular permeability at 5 hours. Brain edema, BBB permeability, and serotonin levels were not attenuated when the compound was administered 60 minutes post-CHI suggesting that HO is involved in cellular and molecular mechanisms of edema formation and BBB breakdown early after CHI.

DNA synthesis and thymidine kinase activity of rat colon epithelial cells fractionated by discontinuous Ficoll gradient.

Epithelial cells from colons of adult Sprague-Dawley rats were fractionated on a discontinuous Ficoll gradient at low centrifugal forces (170 x g) for approximately 60 minutes. Epithelial cells were separated into three distinct zones, whereas cell debris, yeast, and bacteria remained at the top of the gradient. The percentage of cells in each zone was inversely related to the density of the gradient. More than 95% of the cells were morphologically intact and viable (excluded trypan blue). Cells sedimenting at higher densities of Ficoll exhibited higher thymidine kinase activity and DNA synthesis, suggestive of active cell division. The cells sedimenting at lower densities of Ficoll showed the least thymidine kinase activity and DNA synthesis, properties that are compatible with those of mature absorptive cells. Tall columnar cells with vesicular nuclei were predominant in the fraction sedimenting at the lowest density (top fraction). At higher densities (middle and lower fractions), most of the cells were short and columnar with basally located condensed dark-staining nuclei.

Dosimetric comparison of three dimensional conformal radiation therapy versus intensity modulated radiation therapy in accelerated partial breast irradiation.

AIM OF STUDY: Breast conserving surgery (BCS) is the standard treatment for stage I and II breast cancer. Multiple studies have shown that recurrences after lumpectomy occur mainly in or near the tumor bed. Use of accelerated partial breast irradiation (APBI) allows for significant reduction in the overall treatment time that results in increasing patient compliance and decreasing healthcare costs. We conducted a treatment planning study to evaluate the role of intensity modulated radiation therapy (IMRT) with regards to three-dimensional conformal radiation therapy (3DCRT) in APBI. MATERIALS AND METHODS: Computed tomography planning data sets of 33 patients (20 right sided and 13 left sided) with tumor size less than 3 cm and negative axillary lymph nodes were used for our study. Tumor location was upper outer, upper inner, central, lower inner, and lower outer quadrants in 10, 10, 5, 4 and 4 patients, respectively. Multiple 3DCRT and IMRT plans were created for each patient. Total dose of 38.5 Gy in 10 fractions were planned. Dosimetric analysis was done for the best 3DCRT and IMRT plans. RESULTS: The target coverage has been achieved by both the methods but IMRT provided better coverage (P = 0.04) with improved conformity index (P = 0.01). Maximum doses were well controlled in IMRT to below 108% (P < 0.01). Heart V2 Gy (P < 0.01), lung V5 Gy (P = 0.01), lung V10 Gy (P = 0.02), contralateral breast V1 Gy (P < 0.01), contralateral lung V2 Gy (P < 0.01), and ipsilateral uninvolved breast (P < 0.01) doses were higher with 3DCRT compared to IMRT. CONCLUSION: Dosimetrically, IMRT-APBI provided best target coverage with less dose to normal tissues compared with 3DCRT-APBI.

E. coli-based in vitro transcription/translation: in vivo-specific synthesis rates and high yields in a batch system.

A highly efficient Escherichia coli-based, batch in vitro protein synthesis system using circular plasmid DNA is described. Compared to a presently available commercial kit, this improved system produced several hundredfold greater yields of the rDNA human protein thrombopoietin (ca. 450 micrograms/mL). The system is capable of obtaining specific synthesis rates similar to those in vivo, approximately a 1000-fold increase compared to the original methods previously described. It compares favorably in rates and yields to the recently published semicontinuous methods but with the convenience of a true batch system.

Alteration of the biochemical valves in the central metabolism of Escherichia coli.

Although E. coli central metabolism has been studied for several decades, many regulatory features are still unknown. To achieve the goal of rational manipulation of cellular metabolism, it is important to understand how E. coli responds to overexpressed enzymes. By studying the biochemical control of fluxes between PEP, pyruvate, and OAA, we have addressed some fundamental questions that may prove to be essential for applications in metabolic engineering. First, we found that simultaneous overexpression of Pck and Ppc, or Pps alone in the presence of glucose leads to phenotypes consistent with futile cycline. In contrast to our expectation, futile cycling per se does not affect the growth rate significantly. However, excessive futile cycling may cause competitive disadvantage in the natural environment. Overexpression of Pck caused growth inhibition but no futile cycling. Therefore, E. coli controls the expression of gluconeogenic enzymes not only to avoid excessive futile cycling, but also to prevent toxicity effects. In metabolic engineering, futile cycling may be used as a strategy to stimulate metabolism for either production of metabolites or digestion of toxic wastes. Second, we found that the expression levels of Pps and Pck in E. coli are not optimal for growth on pyruvate and succinate, respectively. Overexpression of these enzymes increases the growth rate on pyruvate and on succinate, respectively, indicating that the slow growth rates on these substrates are at least partially caused by the insufficient supply of PEP and its derivatives. Moreover, E. coli also has not optimized the Ppc level for optimal growth yield on glucose in uncontrolled batch cultures. These results demonstrate that the central metabolism is not optimized for growth under defined laboratory conditions. Thus, the possibility exists that adjustment of native enzyme levels in the central metabolism can improve bioreactor performance. Third, we found that overexpression of Pck affects the transcriptional levels of unrelated genes. This example indicates that physiological responses to enzyme (over)expression should be interpreted cautiously, as changing the expression level of a specific enzyme may affect many unlinked genes. Similar results have also been obtained by use of two-dimensional electrophoresis of proteins from E. coli. Although more questions remain to be answered, fast progress in the area of metabolic engineering can be expected in the near future.

Isolation and HPLC of N-epsilon-lithocholyl lysine as its fluorescamine and dimethylaminoazobenzene isothiocyanate derivatives.

N-epsilon-lithocholyl lysine (NELL) is a component of tissue-bound lithocholic acid (TBL). The isolation of NELL from native protein sources was simulated by hydrolysis of lithocholyl-bovine serum albumin (BSA) (synthesized by coupling lithocholyl-N-hydroxysuccinimide to fatty acid-free BSA) by digestion with a mixture of 6N HCl-propionic acid at 70 C for 3 h under partial vacuum. NELL was isolated on a reversed phase Sep-Pak C18 column and converted to either a fluorophor with fluorescamine or to a chromophor with dimethylaminoazobenzene isothiocyanate for subsequent HPLC using appropriate fluorescence or UV/visible absorption detectors. The procedure described here is quantitative, highly sensitive, and not dependent upon the use of Clostridial cholanoylamino acid hydrolase, the activity of which is sometimes blocked by steric hindrance on the substrate. Using this procedure we have demonstrated the presence of TBL in native histones.

Mean difference vs. variability reduction: tradeoffs in aggregate measures for individual bioequivalence. FDA Individual Bioequivalence Working Group.

Aggregate criteria for individual bioequivalence allow a tradeoff between difference in average bioavailability and reduction in within-subject variability. That is, a large difference in the average bioavailability between a test and a reference formulation can be offset by a sufficient reduction in variability of the test formulation. This offset could allow the test formulation to pass many individual bioequivalence criteria. We have identified 4 possible approaches for dealing with this tradeoff issue: say "No problem," since a reduction in variability is desirable; use disaggregate criteria; use general weighted forms of the individual bioequivalence criteria that weight the variance terms; and change the acceptable upper limits to reduce the impact of scaling to the reference formulation's within-subject variability. A dataset with a 14% increase in average bioavailability and a 48% reduction in within-subject standard deviation is used as an example of these issues.

Blockade of histamine H2 receptors attenuate blood-brain barrier permeability, cerebral blood flow disturbances, edema formation and cell reactions following hyperthermic brain injury in the rat.

Role of histamine H2 receptors in blood-brain barrier (BBB) disturbances, cerebral blood flow (CBF), brain edema formation, and cell injury caused by heat stress in a rat model was examined using the pharmacological approach. Blockade of histamine H2 receptors by cimetidine or ranitidine significantly attenuated the BBB permeability to Evans blue albumin and [131]I-sodium extravasation, brain edema formation and cell injury following 4 h heat stress in rats at 38 degrees C. These drug treatments also restored the CBF to near normal values. These beneficial effects in heat stress were most marked in rats treated with ranitidine compared to cimetidine given in identical dosage. Our observations suggest that blockade of histamine H2 receptor is beneficial in hyperthermic brain injury and indicates that histamine is involved in the pathophysiology of heat stress induced brain dysfunction. Our study strongly suggests further need to develop more specific and sensitive histaminergic H2 receptor blockers for the treatment of neurological ailments.

Fluticasone propionate (0.05%) cream compared to betamethasone valerate (0.12%) cream in the treatment of steroid-responsive dermatoses: a multicentric study.

Fluticasone propionate is a new topical steroid developed as a result of modification of the 19-carbon androstane structure. In the present study, efficacy of this steroid was compared with betamethasone valerate cream in patients with psoriasis and eczema. Though fluticasone propionate was marginally more effective than betamethasone valerate, this difference was not statistically significant.

Radon emanation from backfilled mill tailings in underground uranium mine.

Coarser mill tailings used as backfill to stabilize the stoped out areas in underground uranium mines is a potential source of radon contamination. This paper presents the quantitative assessment of radon emanation from the backfilled tailings in Jaduguda mine, India using a cylindrical accumulator. Some of the important parameters such as (226)Ra activity concentration, bulk density, bulk porosity, moisture content and radon emanation factor of the tailings affecting radon emanation were determined in the laboratory. The study revealed that the radon emanation rate of the tailings varied in the range of 0.12-7.03 Bq m(-2) s(-1) with geometric mean of 1.01 Bq m(-2) s(-1) and geometric standard deviation of 3.39. An increase in radon emanation rate was noticed up to a moisture saturation of 0.09 in the tailings, after which the emanation rate gradually started declining with saturation due to low diffusion coefficient of radon in the saturated tailings. Radon emanation factor of the tailings varied in the range of 0.08-0.23 with the mean value of 0.21. The emanation factor of the tailings with moisture saturation level over 0.09 was found to be about three times higher than that of the absolutely dry tailings. The empirical relationship obtained between (222)Rn emanation rate and (226)Ra activity concentration of the tailings indicated a significant positive linear correlation (r = 0.95, p < 0.001). This relationship may be useful for quick prediction of radon emanation rate from the backfill material of similar nature.

Assessment of (222)Rn emanation from ore body and backfill tailings in low-grade underground uranium mine.

This paper presents a comparative study of (222)Rn emanation from the ore and backfill tailings in an underground uranium mine located at Jaduguda, India. The effects of surface area, porosity, (226)Ra and moisture contents on (222)Rn emanation rate were examined. The study revealed that the bulk porosity of backfill tailings is more than two orders of magnitude than that of the ore. The geometric mean radon emanation rates from the ore body and backfill tailings were found to be 10.01 × 10(-3) and 1.03 Bq m(-2) s(-1), respectively. Significant positive linear correlations between (222)Rn emanation rate and the (226)Ra content of ore and tailings were observed. For normalised (226)Ra content, the (222)Rn emanation rate from tailings was found to be 283 times higher than the ore due to higher bulk porosity and surface area. The relative radon emanation from the tailings with moisture fraction of 0.14 was found to be 2.4 times higher than the oven-dried tailings. The study suggested that the mill tailings used as a backfill material significantly contributes to radon emanation as compared to the ore body itself and the (226)Ra content and bulk porosity are the dominant factors for radon emanation into the mine atmosphere.