1-D MOF [Ag2(C10H10N3O3S)2(C4H8N)2]n: photocatalytic treatment, crystallographic evaluation, ADMET parameters, CT-DNA and anticancer activity.

Newly synthesized dinuclear crystalline polymer, the silver complex of bidentate Sulfamethoxazole (Ag-SMX) in the presence of secondary ligand pyrrolidine has been characterized by elemental, spectral (1H-NMR spectra, FT-IR spectra, UV-Vis spectra.), powder XRD, and single-crystal X-ray diffraction (single-crystal) analysis. The synthesis molecular structure of the dinuclear [Ag2(C10H10N3O3S)2(C4H8N)2]n complex reveals a one-dimensional polymeric chain with seesaw geometry (τ4 = 0.71): two silvers interlink each other by argentophilic interaction with Ag1…Ag2 separation distance of 3.0047(6) Å. The Hirshfeld surfaces (HS) and 2D fingerprint plots were used to examine the interconnects in the crystal packing. Molecule properties including MEP, MPA, HOMO-LUMO energy, and global reactivity descriptor parameters were computed to understand the molecule's stability. From ADMET parameters, human Intestinal Absorbance data revealed that the compound has the potential to be well absorbed, and also Ag-smx complex cannot cross the blood-brain barrier (BBB). The capacity of the silver complex to interact with CtDNA was investigated using absorption spectroscopy and viscosity tests. The interaction between CT-DNA reveals that the Ag-SMX complex exhibits the strongest binding affinity among all known sulfonamide derivatives and their metal complexes. The silver complex has higher inhibitory action than the free SMX ligand, according to data from a panel of gram (+ve) and gram (-ve) organisms' minimum inhibitory concentrations. In vitro cytotoxicity investigation revealed that the IC50 value for Ag-SMX is 57.12 g/mL and for SMX is 100.90 g/mL against human lung cancer cell line (A549). This study revealed that, when compared to SMX free-ligand, Ag-SMX is the most effective in terms of cytotoxicity toward the human lung cancer cell line (A549 cell line). In under 120 min, the synthesized Ag-smx complex showed exceptional photo-degradation characteristics against methylene blue (MB) (10 ppm) in visible light radiation.Communicated by Ramaswamy H. Sarma.

Visible light-driven photocatalysts, quantum chemical calculations, ADMET-SAR parameters, and DNA binding studies of nickel complex of sulfadiazine.

A 3D-supramolecular nickel integrated Ni-SDZ complex was synthesized using sodium salt of sulfadiazine as the ligand and nickel(II) acetate as the metal salt using a condensation process and slow evaporation approach to growing the single crystal. The metal complex was characterized for its composition, functional groups, surface morphology as well as complex 3D structure, by resorting to various analytical techniques. The interacting surface and stability as well as reactivity of the complex were carried out using the DFT platform. From ADMET parameters, human Intestinal Absorbance data revealed that the compound has the potential to be well absorbed, and also Ni-SDZ complex cannot cross the blood-brain barrier (BBB). Additionally, the complex's DNA binding affinity and in-vivo and in-vitro cytotoxic studies were explored utilizing UV-Vis absorbance titration, viscosity measurements, and S. pombe cells and brine shrimp lethality tests. In visible light radiation, the Ni-SDZ complex displayed exceptional photo-degradation characteristics of approximately 70.19% within 70 min against methylene blue (MB).

A Case of Refractory Pulmonary Coccidioidomycosis Successfully Treated with Posaconazole Therapy.

Coccidioidomycosis is an endemic fungal infection caused by the inhalation of the spores of Coccidioides species. Patients with underlying immunosuppressive illness can contract chronic or disseminated disease which requires prolonged systemic therapy. Pulmonary coccidioidomycosis remains as an illusory and abstruse disease, with increased prevalence that poses as a challenge for clinicians in developing an effective strategy for treatment. Here, we report successful treatment of a refractory case of chronic relapsing pulmonary coccidioidomycosis in a 50-year old woman with a thin-walled cavitary lung lesion who was ultimately treated with posaconazole.

NSC-87877 inhibits DUSP26 function in neuroblastoma resulting in p53-mediated apoptosis.

Dual specificity protein phosphatase 26 (DUSP26) is overexpressed in high-risk neuroblastoma (NB) and contributes to chemoresistance by inhibiting p53 function. In vitro, DUSP26 has also been shown to effectively inhibit p38 MAP kinase. We hypothesize that inhibiting DUSP26 will result in decreased NB cell growth in a p53 and/or p38-mediated manner. NSC-87877 (8-hydroxy-7-[(6-sulfo-2-naphthyl)azo]-5-quinolinesulfonic acid), a novel DUSP26 small molecule inhibitor, shows effective growth inhibition and induction of apoptosis in NB cell lines. NB cell lines treated with small hairpin RNA (shRNA) targeting DUSP26 also exhibit a proliferation defect both in vitro and in vivo. Treatment of NB cell lines with NSC-87877 results in increased p53 phosphorylation (Ser37 and Ser46) and activation, increased activation of downstream p38 effector proteins (heat shock protein 27 (HSP27) and MAP kinase-activated protein kinase 2 (MAPKAPK2)) and poly ADP ribose polymerase/caspase-3 cleavage. The cytotoxicity resulting from DUSP26 inhibition is partially reversed by knocking down p53 expression with shRNA and also by inhibiting p38 activity with SB203580 (4-[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine). In an intrarenal mouse model of NB, NSC-87877 treatment results in decreased tumor growth and increased p53 and p38 activity. Together, these results suggest that DUSP26 inhibition with NSC-87877 is an effective strategy to induce NB cell cytotoxicity in vitro and in vivo through activation of the p53 and p38 mitogen-activated protein kinase (MAPK) tumor-suppressor pathways.

An in vitro evaluation of the effect of laser irradiation on the thrombogenicity of thrombus.

The effect of laser irradiation on the thrombogenicity of thrombus was evaluated by treating thrombi, formed in-vitro from canine blood, with two different doses of cw Nd:YAG laser energy at 1064 nm. The thrombi were then incubated with whole blood, and the plasma levels of fibrinogen and thrombin-antithrombin III-complexes were measured. A statistically significant decrease (p < 0.05) in the thrombogenicity was indicated by a reduction in both fibrinogen consumption and levels of thrombin-antithrombin III-complexes in the high dose group (600 joules, 100 degrees C peak temperature) in comparison to the low dose group (300 joules, 70 degrees C peak temperature) and the untreated thrombi. These findings suggest that laser irradiation of thrombus at an appropriate dose may substantially reduce its thrombogenicity and ability to modulate hemostasis.

Estimation of in situ ultrasound exposure during obstetric examinations.

Layered tissue models are developed to estimate in situ ultrasound intensity during common obstetric examinations by incorporation of measured overlying tissue thicknesses with data on the attenuation properties of tissues. Results are compared with attenuation models recommended by the United States Food and Drug Administration (FDA) and National Council on Radiation Protection and Measurements (NCRP). For abdominal and transvaginal scanning in the first trimester, fixed attenuation models based on attenuation values of 1.2 dB/MHz and 0.6 dB/MHz, respectively, are representative of worst-case exposure conditions. For second and third trimesters, a fixed attenuation value of 0.8 dB/MHz is representative of worst-case exposure conditions. A fixed attenuation value of 1.0 dB/MHz is suggested for common Doppler examinations. The study suggests that the FDA-derating factor of 0.3 dB/cm.MHz may not give a conservative estimate of in situ intensity for certain obstetric examinations.

The effect of mesterolone on sperm count, on serum follicle stimulating hormone, luteinizing hormone, plasma testosterone and outcome in idiopathic oligospermic men.

Two hundred fifty subfertile men with idiopathic oligospermia (count less than 20 million/ml) were treated with mesterolone (100-150 mg/day) for 12 months. Seminal analysis were assayed 3 times and serum follicle stimulating hormone (FSH) luteinizing hormone (LH) and plasma testosterone were assayed once before treatment and repeated at 3, 6, 9 and 12 months after the initiation of treatment. One hundred ten patients (44%) had normal serum FSH, LH and plasma testosterone, 85 patients (34%) had low serum FSH, LH and low plasma testosterone. One hundred seventy-five patients (70%) had moderate oligospermia (count 5 to less than 20 million/ml) and 75 patients (30%) had severe oligospermia (count less than 5 million/ml). Seventy-five moderately oligospermic patients showed significant improvement in the sperm density, total sperm count and motility following mesterolone therapy whereas only 12% showed improvement in the severe oligospermic group. Mesterolone had no depressing effect on low or normal serum FSH and LH levels but had depressing effect on 25% if the levels were elevated. There was no significant adverse effect on testosterone levels or on liver function. One hundred fifteen (46%) pregnancies resulted following the treatment, 9 of 115 (7.8%) aborted and 2 (1.7%) had ectopic pregnancy. Mesterolone was found to be more useful in patients with a sperm count ranging between 5 and 20 million/ml. Those with severe oligospermia (count less than 5 million) do not seem to benefit from this therapy.

Outcome of pregnancy following investigation and treatment of infertility.

We studied 500 women who conceived after investigation and treatment for different infertility problems and compared the outcome of the 5 infertility groups (Group 1 to 5), the ovulatory dysfunction (Group 1), male infertility (Group 2), A.I.D. (Group 3), tubal surgery and IVF (Group 4) and no treatment (Group 5) with the outcome in the hospital group during a period of 3 years. The incidence of abortion in Group 3 is significantly higher (13.8%), the incidence of ectopic pregnancy is significantly higher in Group 4 (21.7%) as compared with the incidence in the hospital group (P less than 0.01). The rate of pre-existing hypertension and gestational diabetes is significantly higher in all the 5 infertility groups as compared with the incidence in the hospital group (P less than 0.05). The incidence of preterm labor in general is less in the infertility group as compared with the incidence in the hospital group (P greater than 0.05). The incidence of older women, multiple pregnancy, induction of labor, operative deliveries, fetal distress, low Apgar score, babies with birth weight below the tenth centile were higher in the infertility groups (P less than 0.05). But the perinatal mortality or major or minor fetal anomalies were not significantly different in the infertility groups as compared with the rate in the hospital groups (P greater than 0.05).

Combined intrauterine and extrauterine gestation: a report of case history and review.

Combined intrauterine and extrauterine gestation is very rare. There is a higher maternal morbidity and fetal loss, due to delayed or missed diagnosis. We present a patient who was treated for primary infertility with ovulation induction agents, who presented later with combined intra- and extra-uterine gestation with successful outcome following delivery of a healthy male infant at 38 weeks gestation.

Estrogen treatment and subsequent pregnancy in two patients with severe hypergonadotropic ovarian failure.

The history, diagnosis and management of two patients with premature ovarian failure who responded to estrogen replacement therapy is presented. Both women conceived and had a live healthy baby.

Effect of hormone replacement therapy on anti-thrombin III activity in post menopausal women.

Anti-thrombin III is the major inhibitor of activated blood clotting factors. We studied 320 patients with climacteric symptoms who received estrogen replacement therapy to assess the effect of hormone therapy on Anti-thrombin III (AT-III) activity). Of the 320 patients 80 patients received Prempak C (0.625 mg) for 2 years, 82 patients received Prempak C (1.25 mg) for 2 years, 78 patients received Cycloprogynova (1 mg) for 2 years and the remaining 80 patients received Cycloprogynova (2 mg) for 2 years. The mean AT-III activity before, during and 3 months after treatment showed no significant difference in all the four groups of patients. There was no incidence of myocardial infarction or stroke or thrombo-embolic disease in this group of 320 patients receiving estrogen replacement therapy.

Ultrasonic assessment of ovulation in cyclofenil induced ovulatory cycles.

Graafian follicle growth was studied by ultrasound scanning during the peri-ovulatory period in 64 ovulatory cycles in 32 infertile patients on cyclofenil treatment, and compared with a control group of 32 patients with confirmed ovulatory cycles assessed on the basis of serum progesterone levels in the middle of the second half of the cycle. The mean maximum diameters of the leading follicles before ovulation were 21.9 +/- 0.6 (S.E.) mm and 24.4 +/- 0.5 (S.E.) mm, respectively for the cyclofenil group and the normal control group (P greater than 0.05). In 79% of the cyclofenil stimulated group and 83% of the spontaneous ovulation group, ultrasonic evidence of ovulation was present between 12 and 36 h after the initial increase in urine LH levels. Ultrasound scanning was found to be simple, and a quick method of monitoring graafian follicle development and ovulation on cyclofenil therapy and the cycles were comparable to the spontaneous ovulatory cycles as assessed on the basis of graafian follicle diameter, and the time of ovulation. Cervical score was not found to be useful to assess ovulation time in the cyclofenil treated group since 31.3% achieved a score of 10 or more on day -4, 93.8% within 24 h of ovulation and 24% on day 3 following the ovulation.

Virilization due to a rare ovarian tumor in a postmenopausal woman.

A 60-year-old postmenopausal woman presented with evidence of hirsutism, alopecia and mild virilization. Clinical examination and biochemical abnormalities suggested that the source of androgen excess was ovarian, and an ovarian tumor was confirmed and removed at laparotomy followed by normal endocrine profile in the postoperative period.

Ultrasonic assessment of cervix in "at risk" patients.

One hundred seventy patients were considered to be at risk of cervical incompetence from their previous history. They were scanned serially from the first trimester to 36 weeks gestation. Of the 170, 105 patients (61.8%) were found to have defective cervix (the length of cervix, width of the cervix, and cervical canal at the level of the internal cervical os, and herniation of amniotic membrane with or without fetal parts into the cervical canal). Of the 105 patients diagnosed to have defective cervix (possible cervical incompetence), 22 patients (21%) aborted, 48 patients (45.7%) had to have cervical cerclage, 26 patients (24.8%) had preterm delivery and the remaining 9 patients (8.5%) had no problems during pregnancy. The remaining 65 patients (38.2%) did not have ultrasonic evidence of cervical incompetence and 3 aborted and only 2 patients delivered between 35 and 37 weeks gestation while 60 patients delivered between 37 and 42 weeks gestation. These 65 patients would have had cervical cerclage on the basis of the clinical history alone, but in only 6, cervical cerclage was inserted.

The effects of Cyclofenil on the Cervical Mucus Score (Insler).

Daily simultaneous cervical mucus evaluation and ultrasonography of the Graafian follicular growth and ovulation were studied (in the mid-cycle) in 8 infertile British women during 30 Cyclofenil-stimulated cycles, and compared with 18 non-stimulated normal ovulatory cycles in 12 subjects (controls). In the 16 Cyclofenil-induced ovulatory cycles, there was an early (5 days prior to the day of ultrasonic ovulation) Full Cervical Mucus Score (Insler) in 69% of the cycles, and the Full Cervical Mucus Score lasted for 7 days or more in 63% of the cycles. In 38%, there was persistence of the Full Cervical Mucus Score on the third day after ultrasonic ovulation. In the 14 Cyclofenil-treated anovulatory cycles, a Full Cervical Mucus Score was recorded on one or more occasions in the mid-cycle in 29% of the cycles. The classical teaching of prediction of the probable timing of ovulation by Cervical Mucus Scoring is not applicable to Cyclofenil-stimulated cycles.

Ultrasound evaluation of amniotic fluid: outcome of pregnancies with severe oligohydramnios.

We studied a group of 247 patients out of 7725 patients who had an ultrasonic examination between 32 and 36 weeks gestation and were found to have oligohydramnios (amniotic fluid volume (AFV) less than or equal to 2.0 cm). We compared the features of labor and mode of delivery and perinatal outcome in this group with that of a normal control group of 247 patients who also had an ultrasonic examination between 32 and 36 weeks gestation and were found to have normal AFV (greater than 2.0 to less than 8.0 cm). The incidence of induction of labor, of elective cesarean section, of preterm delivery (less than 37 weeks' gestation) was significantly higher in the oligohydramnios group (study group) as compared with the incidence in the control group (P less than 0.05). The incidence of fetal distress in antenatal and intrapartum period, pH (less than or equal to 7.2), of low Apgar score (0-5), of intrauterine growth retardation (IUGR) (less than tenth centile) infants, of major fetal anomaly and perinatal mortality rate (PNMR) are significantly higher in the oligohydramnios group as compared with the incidence and PNMR in the normal control group (P less than 0.05). The ultrasonic finding of oligohydramnios should alert the clinician regarding the possibility of problems in labor and perinatal period.

The relationship of increased amniotic fluid volume to perinatal outcome.

We studied a group of 135 patients with polyhydramnios diagnosed on the basis of ultrasonic findings (greatest vertical diameter of the liquor column greater than or equal to 8.0 cm) between 32 and 36 weeks gestation (study group). We compared the obstetric characteristics and perinatal outcome of the study group with a similar number who constituted our control group. The incidence of women aged 20 years or less was higher in the study group (8.9%) compared with 4.5% in the control group. Of the 135 patients who were diagnosed to have polyhydramnios ultrasonically, the clinical diagnoses prior to referral for ultrasonic scanning, were, suspected large for date fetuses in 34 patients (25.2%), clinically suspected polyhydramnios in 28 (20.7%), gestational diabetes in 21 (15.6%) and insulin dependent diabetes in 6 (4.4%) compared with 13.3%, 5.2%, 3.0% and 0.7%, respectively in the control group (P less than 0.05). Preterm delivery occurred in 11.1% in the study group compared with the incidence of 6.7% in the control group. The incidence of fetal distress, low Apgar Score, macrosomic infants, major fetal anomalies, gross and corrected perinatal mortality rate and admission to special/intensive care nursery was significantly higher in the study group compared with that of the control (P less than 0.01). We found ultrasonic examination is a reliable technique to assess the amount of amniotic fluid volume and it alerts the clinician to possible future problems in pregnancy, labor and neonatal period.

USP7 inhibitor P22077 inhibits neuroblastoma growth via inducing p53-mediated apoptosis.

Neuroblastoma (NB) is a common pediatric cancer and contributes to more than 15% of all pediatric cancer-related deaths. Unlike adult tumors, recurrent somatic mutations in NB, such as tumor protein 53 (p53) mutations, occur with relative paucity. In addition, p53 downstream function is intact in NB cells with wild-type p53, suggesting that reactivation of p53 may be a viable therapeutic strategy for NB treatment. Herein, we report that the ubiquitin-specific protease 7 (USP7) inhibitor, P22077, potently induces apoptosis in NB cells with an intact USP7-HDM2-p53 axis but not in NB cells with mutant p53 or without human homolog of MDM2 (HDM2) expression. In this study, we found that P22077 stabilized p53 by inducing HDM2 protein degradation in NB cells. P22077 also significantly augmented the cytotoxic effects of doxorubicin (Dox) and etoposide (VP-16) in NB cells with an intact USP7-HDM2-p53 axis. Moreover, P22077 was found to be able to sensitize chemoresistant LA-N-6 NB cells to chemotherapy. In an in vivo orthotopic NB mouse model, P22077 significantly inhibited the xenograft growth of three NB cell lines. Database analysis of NB patients shows that high expression of USP7 significantly predicts poor outcomes. Together, our data strongly suggest that targeting USP7 is a novel concept in the treatment of NB. USP7-specific inhibitors like P22077 may serve not only as a stand-alone therapy but also as an effective adjunct to current chemotherapeutic regimens for treating NB with an intact USP7-HDM2-p53 axis.

Changes in fiber tract integrity and visual fields after anterior temporal lobectomy.

OBJECTIVE: To investigate postoperative changes in fiber tract integrity in patients with temporal lobe epilepsy (TLE) following anterior temporal lobectomy (ATL) and to determine whether postoperative changes are 1) stable vs progressive and 2) related to visual field defects. METHODS: Diffusion tensor imaging (DTI) was obtained in 7 patients with TLE before, 2 months after, and 1 year after ATL. Changes in fractional anisotropy (FA) were evaluated in a whole-brain voxel-wise analysis, as well within specific fiber tracts. Repeated-measures analysis of variance was performed to examine the time course of FA changes within ipsilateral and contralateral fiber tracts. Quantitative visual field analysis was performed to determine whether decreases in regional FA were related to the extent or location of visual field defects. RESULTS: Patients showed decreased FA 2 months post-ATL in ipsilateral fiber tracts transected during surgery (parahippocampal cingulum, uncinate fasciculus, inferior longitudinal fasciculus, and fornix), as well as in fiber tracts not directly transected (inferior fronto-occipital fasciculus and corpus callosum). Additional decreases in FA were not observed from 2 months to 1 year post-ATL. Visual field defects in most patients were characterized by incomplete quadrantanopsias. However, FA reductions in one patient extended into temporo-occipital cortex and the splenium of the corpus callosum and were associated with a complete hemianopia. CONCLUSIONS: Wallerian degeneration is apparent 2 months following unilateral ATLs in ipsilateral fibers directly and indirectly affected during surgery. These changes do not appear to progress over the course of a year, but may correlate with the nature and extent of postoperative visual field defects.