Remediation of textile azo dye acid red 114 by hairy roots of Ipomoea carnea Jacq. and assessment of degraded dye toxicity with human keratinocyte cell line.

Bioremediation has proven to be the most desirable and cost effective method to counter textile dye pollution. Hairy roots (HRs) of Ipomoea carnea J. were tested for decolourization of 25 textile azo dyes, out of which >90% decolourization was observed in 15 dyes. A diazo dye, Acid Red 114 was decolourized to >98% and hence, was chosen as the model dye. A significant increase in the activities of oxidoreductive enzymes was observed during decolourization of AR114. The phytodegradation of AR114 was confirmed by HPLC, UV-vis and FTIR spectroscopy. The possible metabolites were identified by GCMS as 4- aminobenzene sulfonic acid 2-methylaniline and 4- aminophenyl 4-ethyl benzene sulfonate and a probable pathway for the biodegradation of AR114 has been proposed. The nontoxic nature of the metabolites and toxicity of AR114 was confirmed by cytotoxicity tests on human keratinocyte cell line (HaCaT). When HaCaT cells were treated separately with 150 µg mL(-1) of AR114 and metabolites, MTT assay showed 50% and ≈100% viability respectively. Furthermore, flow cytometry data showed that, as compared to control, the cells in G2-M and death phase increased by 2.4 and 3.6 folds respectively on treatment with AR114 but remained unaltered in cells treated with metabolites.

Characterization of phytochemicals and evaluation of anti-cancer potential of Blumea eriantha DC.

The aim of the present study was to evaluate the in vitro anti-cancer and anti-oxidant potential of methanol extract of Blumea eriantha as well as its phytochemical characterization. The in vitro cytotoxic and antiproliferative activities of B. eriantha methanolic extract of leaves were evaluated using MTT assay on HeLa and B16F10 cell lines, and wound scratch and colony formation assays on B16F10 cell lines. The expressions of p53 and Bcl-2 genes were also determined by reverse transcriptase-polymerase chain reaction to establish apoptosis. Isolation and identification of chemical constituents were carried out by various chromatographic and spectroscopic analytical techniques including HPTLC and LC-MS. The methanol extract of the leaves of B. eriantha showed potent in vitro antioxidant and anticancer properties. Moreover, the extract showed significant loss of wound healing, thus suggesting that it could prevent a possible metastasis. Hence, B. eriantha could be explored as a potential anticancer plant with antimetastatic properties.

Gas-forming liver abscess in a patient with multi-organ failure: role of imaging and management.

We present an unusual case of air-containing liver abscess demonstrated on plain film and ultrasonography with successful treatment utilizing ultrasound-guided drainage in a patient in septic shock. Although surgical drainage is often indicated, ultrasound-guided catheter drainage along with supportive antibiotic therapy can be a safe treatment alternative in critical patients.

Design and evaluation of self-nanoemulsifying pellets of repaglinide.

The aim of study was to develop self-nanoemulsifying pellets (SNEP) for oral delivery of poorly water soluble drug, repaglinide (RPG). Solubility of RPG in oily phases and surfactants was determined to identify components of self-nanoemulsifying drug delivery system (SNEDDS). The surfactants and cosurfactants were screened for their ability to emulsify oily phase. Ternary phase diagrams were constructed to identify nanoemulsification area for the selected systems. SNEDDS formulations with globule size less than 100 nm were evaluated for in vivo anti-hyperglycemic activity in neonatal streptozotocin rat model. A significant reduction in glucose levels was produced by optimized SNEDDS formulation in comparison to the control group. The optimized SNEDDS formulations were pelletized via extrusion/spheronization technique using microcrystalline cellulose and lactose. SNEP were characterized by X-ray powder diffraction and scanning electron microscopy. X-ray diffraction study indicated loss of crystallinity of RPG in SNEP. The SNEP exhibited good flow properties, mechanical strength and formed nanoemulsion with globule size less than 200 nm. SNEP showed in vitro release of more than 80% RPG in 10 min which was significantly higher than RPG containing reference pellets. In conclusion, our studies illustrated that RPG, a poorly water soluble drug can be successfully formulated into SNEP which can serve as a promising system for the delivery of poorly water soluble drugs.

Morphine pharmacokinetics and pharmacodynamics in preterm and term neonates: secondary results from the NEOPAIN trial.

BACKGROUND: Relationships between plasma morphine concentrations and neonatal responses to endotracheal tube (ETT) suctioning are unknown in preterm neonates. METHODS: Ventilated preterm neonates (n=898) from 16 centres were randomly assigned to placebo (n=449) or morphine (n=449). After an i.v. loading dose (100 microg kg(-1)), morphine infusions [23-26 weeks postmenstrual age (PMA) 10 microg kg(-1) h(-1); 27-29 weeks 20 microg kg(-1) h(-1); and 30-32 weeks 30 microg kg(-1) h(-1)] were established for a maximum of 14 days. Open-label morphine (20-100 microg kg(-1)) was given for pain or agitation. Morphine assay and neonatal response to ETT suctioning was measured at 20-28 and 70-76 h after starting the drug infusion and at 10-14 h after discontinuation of the study drug. The concentration-effect response was investigated using non-linear mixed effects models. RESULTS: A total of 5119 data points (1598 measured morphine concentrations and 3521 effect measures) were available from 875 neonates for analysis. Clearance was 50% that of the mature value at 54.2 weeks PMA (CLmat(50)) and increased from 2.05 litre h(-1) 70 kg(-1) at 24 weeks PMA to 6.04 litre h(-1) 70 kg(-1) at 32 weeks PMA. The volume of distribution in preterm neonates was 190 litre 70 kg(-1) (CV 51%) and did not change with age. There was no relationship between morphine concentrations (range 0-440 microg litre(-1)) and heart rate changes associated with ETT suctioning or with the Premature Infant Pain Profile. CONCLUSIONS: A sigmoid curve describing maturation of morphine clearance is moved to the right in preterm neonates and volume of distribution is increased compared with term neonates. Morphine does not alter the neonatal response to ETT suctioning.

Cytoplasmic localization of BAG-1 in leukoplakia and carcinoma of the tongue: correlation with p53 and c-erbB2 in carcinoma.

BACKGROUND: The present study evaluated the clinical significance of BAG-1, an antiapoptotic protein, in leukoplakia and carcinoma of the tongue. METHODS: BAG-1 expression was evaluated by immunohistochemistry in paraffin-embedded tissues of leukoplakia (n=25) and carcinoma of the tongue (n=61). RESULTS: Cytoplasmic expression was predominantly seen in 80% and 70% of patients with leukoplakia and carcinoma, respectively. BAG-1 expression was found to be significantly lower in tobacco users than in non-tobacco users. BAG-1 expression in tobacco-using leukoplakia and carcinoma patients was compared by grouping the carcinoma patients according to lymph node status and disease stage. Carcinoma patients with tumor-positive lymph nodes had significantly lower BAG-1 expression than patients with negative lymph nodes and leukoplakia. Further, a trend towards an inverse correlation was observed with p53 and c-erbB2. In univariate and multivariate survival analysis, patient subgroups with 2+ or 3+ marker positivity (BAG-1 negativity, p53 and c-erbB2 positivity) had a reduced overall survival compared with patient subgroups with 1+ marker positivity or negativity. CONCLUSION: BAG-1 negativity in association with p53 and c-erbB2 positivity identified a subgroup of tongue cancer patients with an aggressive phenotype. Hence, an antiapoptotic protein, BAG-1, was found to be down-regulated in chewing-tobacco-mediated tongue carcinogenesis.

Prognostic significance of DNA aneuploidy and p21 ras oncoprotein expression in colorectal cancer and their role in the determination of treatment modalities.

The purpose of the present study was to investigate the prognostic significance of DNA ploidy, S-phase fraction and p21 ras oncoprotein expression in patients with colorectal cancer and to correlate these factors with the clinical behavior of the tumors and their response to therapy. Of 79 patients with colorectal cancer 57% (45/79) had early stage disease. Forty-one percent (32/79) had aneuploid tumors while 30% (24/79) of the tumors had a high (>10%) S-phase fraction. p21ras oncoprotein expression was detected in 38% (30/79) of tumors. Patients with aneuploid tumors had a worse prognosis than patients with diploid tumors (p=0.0002). Similarly, patients with high S-phase fraction tumors had a shorter survival than those with low S-phase fraction tumors (p=0.005). No such difference was found between p21 raspositive and p21 ras-negative tumor subgroups. In early stage colorectal cancer, aneuploidy was closely correlated with disease outcome (p=0.029). Early stage patients with diploid tumors who received radiotherapy and chemotherapy had a better prognosis than patients with aneuploid tumors. In conclusion, DNA ploidy is a significant and independent prognostic factor in colorectal cancer. Aneuploidy and genetic alteration of the p21 ras oncoprotein are important in determining the biological aggressiveness of colorectal cancer. Furthermore, DNA ploidy may identify those subgroups of patients with early stage disease who may benefit from more aggressive treatment.

Active transport of nitrofurantoin into human milk.

STUDY OBJECTIVE: To determine the extent to which nitrofurantoin is transferred into human milk. DESIGN: Prospective, single-dose pharmacokinetic study. SETTING: University-affiliated clinical research center. PATIENTS: Four healthy lactating women 8-26 weeks postpartum. INTERVENTION: All subjects received a single, oral, 100-mg dose of nitrofurantoin macrocrystals with food. Serial serum and milk samples were obtained and analyzed by high-performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: Milk pH, milk fat partitioning, and protein binding in serum and milk were determined. Predicted milk:serum ratio (M:S) was compared with the observed M:S. Nitrofurantoin M:S predicted was 0.28+/-0.05, whereas M:S observed was 6.21+/-2.71. Average milk concentration was 1.3 mg/L, and estimated suckling infant dosage was 0.2 mg/kg/day or 6% of maternal dose (mg/kg). CONCLUSIONS: Nitrofurantoin is actively transported into human milk, achieving concentrations in milk greatly exceeding those in serum. Concern is warranted for suckling infants younger than 1 month old, or for infants with a high frequency of glucose-6-phosphate dehydrogenase deficiency or sensitivity to nitrofurantoin.

BDNF regulates the intrinsic excitability of cortical neurons.

Neocortical pyramidal neurons respond to prolonged activity blockade by modulating their balance of inward and outward currents to become more sensitive to synaptic input, possibly as a means of homeostatically regulating firing rates during periods of intense change in synapse number or strength. Here we show that this activity-dependent regulation of intrinsic excitability depends on the neurotrophin brain-derived neurotrophic factor (BDNF). In experiments on rat visual cortical cultures, we found that exogenous BDNF prevented, and a TrkB-IgG fusion protein reproduced, the change in pyramidal neuron excitability produced by activity blockade. Most of these effects were also observed in bipolar interneurons, indicating a very general role for BDNF in regulating neuronal excitability. Moreover, earlier work has demonstrated that BDNF mediates a different kind of homeostatic plasticity present in these same cultures: scaling of the quantal amplitude of AMPA-mediated synaptic inputs up or down as a function of activity. Taken together, these results suggest that BDNF may be the signal controlling a coordinated regulation of synaptic and intrinsic properties aimed at allowing cortical networks to adapt to long-lasting changes in activity.

Plasticity in the intrinsic excitability of cortical pyramidal neurons.

During learning and development, the level of synaptic input received by cortical neurons may change dramatically. Given a limited range of possible firing rates, how do neurons maintain responsiveness to both small and large synaptic inputs? We demonstrate that in response to changes in activity, cultured cortical pyramidal neurons regulate intrinsic excitability to promote stability in firing. Depriving pyramidal neurons of activity for two days increased sensitivity to current injection by selectively regulating voltage-dependent conductances. This suggests that one mechanism by which neurons maintain sensitivity to different levels of synaptic input is by altering the function relating current to firing rate.

Two-color GFP expression system for C. elegans.

We describe the use of modified versions of the Aequora victoria green fluorescent protein (GFP) to simultaneously follow the expression and distribution of two different proteins in the nematode, Caenorhabditis elegans. A cyan-colored GFP derivative, designated CFP, contains amino acid (aa) substitutions Y66W, N146I, M153T and V163A relative to the original GFP sequence and is similar to the previously reported "W7" form. A yellow-shifted GFP derivative, designated YFP, contains aa substitutions S65G, V68A, S72A and T203Y and is similar to the previously described "I0C" variant. Coding regions for CFP and YFP were constructed in the context of a high-activity C. elegans expression system. Previously characterized promoters and localization signals have been used to express CFP and YFP in C. elegans. Filter sets designed to distinguish YFP and CFP fluorescence spectra allowed visualization of the two distinct forms of GFP in neurons and in muscle cells. A series of expression vectors carrying CFP and YFP have been constructed and are being made available to the scientific community.

Housestaff workload and procedure frequency in the neonatal intensive care unit.

OBJECTIVE: To investigate the association of clinical workload and the decision to perform procedures on infants in the neonatal intensive care unit (NICU). DESIGN: Prospective cohort study over one academic year, observing infants exposed to housestaff working under various levels of clinical workload. SUBJECTS: All 31 housestaff rotating on the NICU service during the academic year 1993 to 1994 were observed. A total of 785 infants were admitted to these housestaff. SETTING: One academic Level III intensive care nursery. MEASUREMENTS AND MAIN RESULTS: Clinical workload was operationalized as number of NICU infants cared for by the individual houseofficer on-call each night. The procedures of interest were number of umbilical artery catheters (UACs), intubations, lumbar punctures (LPs), and peripheral phlebotomy performed by the houseofficer on-call. Using multiple linear regression approaches, controlling for the average severity-of-illness of each of the NICU infants, the experience and residency program of the houseofficer on-call, and the individual attending, we found that increased clinical workload (number of NICU infants) resulted in a significantly greater probability that an admitted infant received an umbilical artery catheter (p = .02), but resulted in less probability that any NICU infant received a lumbar puncture (p = .0001) or peripheral phlebotomy (p = .0002). The decision to intubate an infant was not affected by the workload in the NICU. CONCLUSIONS: The clinical workload of housestaff in the NICU can affect decisions to perform procedures on infants in the NICU. For equivalently severely ill infants, there is a greater chance of receiving a UAC and less chance of being phlebotomized or receiving an LP when workload is high. Attending neonatologists need to be sensitive to possible effects of workload on patient care in the NICU.

Occult spinal dysraphism in neonates: assessment of high-risk cutaneous stigmata on sonography.

OBJECTIVE: In this study, we evaluated the incidence of dorsal cutaneous stigmata in a healthy neonate population; we also assessed whether specific types of cutaneous stigmata are associated with underlying spinal dysraphism. SUBJECTS AND METHODS: From July 1993 through December 1996, we prospectively examined term neonates with dorsal cutaneous stigmata. Each neonate underwent spinal sonography and clinical assessment of the cutaneous stigmata. Incidence of dorsal cutaneous stigmata in a healthy neonatal population was determined by dividing the number of neonates with cutaneous stigmata by the total number of neonates examined. RESULTS: The incidence of cutaneous stigmata in the healthy neonate study population was 4.8%. We examined 207 neonates with 216 cutaneous stigmata, the most common of which was the simple midline dimple (74%). None of the neonates with only a simple midline dimple had spinal dysraphism. Of the 207 neonates we examined, 16 had spinal dysraphism. Clinical examination revealed 180 dimples and 36 other types of cutaneous stigmata (e.g., hemangiomas, hairy patches, masses, tails, lesions). Fourteen (39%) of 36 other cutaneous stigmata were positive for spinal dysraphism. Eight (40%) of 20 atypical dimples were positive for spinal dysraphism. Three were large clefts (>5 mm); the remaining five cases were seen in combination with other lesions and were all located more than 2.5 cm from the anus. Six (67%) of the nine neonates with multiple cutaneous stigmata had spinal dysraphism. CONCLUSION: Simple midline dimples are the most commonly encountered dorsal cutaneous stigmata in neonates and indicate low risk for spinal dysraphism. Only atypical dimples are associated with a high risk for spinal dysraphism, particularly those that are large (>5 mm), high on the back (>2.5 cm from the anus), or appear in combination with other lesions. High-risk cutaneous stigmata in neonates include hemangiomas, upraised lesions (i.e., masses, tails, and hairy patches), and multiple cutaneous stigmata.

Neonatal alloimmune thrombocytopenia due to anti-HPA-1b (PLA2)(Zwb). A case report and review.

BACKGROUND: Neonatal alloimmune thrombocytopenia is a rare condition due to passively acquired maternal antibodies directed against paternal platelet antigens inherited by the infant. Only 5 cases have been reported due to antibodies against HPA-1b (PLA2) (Zwb). CASE REPORT: We report a case of neonatal alloimmune thrombocytopenia due to anti-HPA-1b in the second pregnancy of a 26-year-old Caucasian female. The male infant was treated with a 5-day course of intravenous immunoglobulin without complications. We report the HLA phenotype of the infant's mother and summarize the previous case reports due to anti-HPA-1b. CONCLUSION: Based on this case and a review of the literature, intravenous immunoglobulin as well as random donor exchange transfusion and random donor platelet transfusions are effective in the treatment of neonatal alloimmune thrombocytopenia due to anti-HPA-1b. Obvious associations between HLA alleles and sensitization to HPA-1b have not been elucidated.

The relevance of parity to ureteric dilatation.

OBJECTIVE: To assess whether the mild dilatation of the right ureter in women that is sometimes seen on intravenous urography (IVU) represents persistent dilatation after a previous pregnancy. PATIENTS AND METHODS: The intravenous urograms of 71 men, 63 parous and 27 nulliparous women were evaluated prospectively. The two groups of women were divided into those with and without a confirmed history of urinary tract infection (UTI) as the indication for IVU. producing five groups in all. Measurements were taken on both the 5-min and the compressed or release films on each side. RESULTS: There were no significant differences in ureteric diameters among the five groups for the uncompressed right ureter (P=0.23), the left ureter uncompressed (P=0.32) or compressed (P=0.87). For the compressed right ureter, the difference was significant, with the diameters in the parous women with proven UTIs being larger than in the other groups (P=0.043). CONCLUSION: There is a significant increase in the diameter of the compressed right ureter in the group of parous women with a history of proven UTI. Infection or parity alone do not produce this effect: the combination of the two factors is required.

Activity-dependent scaling of quantal amplitude in neocortical neurons.

Information is stored in neural circuits through long-lasting changes in synaptic strengths. Most studies of information storage have focused on mechanisms such as long-term potentiation and depression (LTP and LTD), in which synaptic strengths change in a synapse-specific manner. In contrast, little attention has been paid to mechanisms that regulate the total synaptic strength of a neuron. Here we describe a new form of synaptic plasticity that increases or decreases the strength of all of a neuron's synaptic inputs as a function of activity. Chronic blockade of cortical culture activity increased the amplitude of miniature excitatory postsynaptic currents (mEPSCs) without changing their kinetics. Conversely, blocking GABA (gamma-aminobutyric acid)-mediated inhibition initially raised firing rates, but over a 48-hour period mESPC amplitudes decreased and firing rates returned to close to control values. These changes were at least partly due to postsynaptic alterations in the response to glutamate, and apparently affected each synapse in proportion to its initial strength. Such 'synaptic scaling' may help to ensure that firing rates do not become saturated during developmental changes in the number and strength of synaptic inputs, as well as stabilizing synaptic strengths during Hebbian modification and facilitating competition between synapses.

Nonpathologic ventriculomegaly in the premature intrauterine growth retarded infant.

OBJECTIVE: To determine any neurosonographic differences between premature intrauterine growth retarded (IUGR) neonates and premature appropriate for gestational age (AGA) infants. STUDY DESIGN: We retrospectively reviewed the head sonograms of 36 premature IUGR infants and 32 premature AGA matched controls. RESULTS: Seven of the 36 (19%) IUGR infant head sonograms revealed mild ventriculomegaly with no evidence of hemorrhage or ischemia. Only one of the 32 control scans (3%) had similar findings. Mild ventriculomegaly in the IUGR infant versus the AGA control neonate was statistically significant (p value of 0.05). Follow-up head sonograms (4 to 12 weeks after the initial head sonogram) revealed resolution of the mild ventriculomegaly in five of the seven IUGR infants. Clinically, all of the IUGR infants with mild ventriculomegaly were asymptomatic during their stay in the nursery and in clinical follow-up ranging from 3 to 5 years. CONCLUSION: Mild ventriculomegaly on the head sonograms of asymptomatic premature IUGR infants (with no associated hemorrhage or ischemic change) should be recognized as a transient, nonpathologic finding.

Evaluation of drug information in an Internet newsgroup.

OBJECTIVE: To determine the accuracy and potential harmfulness of the drug information in a newsgroup on the Internet, sci.med.pharmacy. DESIGN: In this cross-sectional study, two independent reviewers analyzed the nonsubjective drug information in this newsgroup. Drug information was classified as correct, incorrect or could not verify. Information was determined to have no harm, minor harm, moderate harm, or severe harm. RESULTS: About one-half of the drug information was found to be correct in this newsgroup. Although 68% of the drug information was found to result in no harm, 19.4% was classified as harmful. CONCLUSIONS: If drug information on the Internet contains inaccuracies, its ready accessibility may pose a public health problem. With the number of Internet users growing, health professionals need to be aware of the potential for dissemination of misinformation, and need to become familiar with the Internet and the various health information resources available to the public.

Relation of gastric distention to prostaglandin therapy in neonates.

PURPOSE: To evaluate the short-term gastric effects of prostaglandin therapy in neonates. MATERIALS AND METHODS: The authors retrospectively reviewed the radiographs of nine neonates with congenital heart disease who received prostaglandins during the 1st week of life. Eighteen matched control infants (nine healthy neonates and nine infants with noncyanotic congenital heart disease) who did not receive prostaglandins were also evaluated. RESULTS: Within 48 hours of initial prostaglandin therapy, persistent (>3 days) gastric distention was noted in four of nine infants. No infants developed feeding intolerance during the 1st week of life; two of nine infants (both with initial asymptomatic gastric distention) developed feeding intolerance with prolonged prostaglandin therapy. In all cases, gastric distention resolved with cessation of prostaglandins. The radiographs of the control infants were unremarkable (P < .01). CONCLUSION: Persistent, asymptomatic gastric distention can be seen in neonates within 48 hours of initiation of prostaglandin therapy. Intervention is not warranted; this finding resolves with cessation of prostaglandins. Early gastric distention may be predictive of feeding intolerance in infants who receive prolonged prostaglandin therapy.