Nuclear Localization Signal Enhances the Targeting and Therapeutic Efficacy of a Porphyrin-Based Molecular Cargo: A Systemic In Vitro and Ex Vivo Evaluation.

The objective of the present work was to evaluate the potential of a nuclear localization signal (NLS) toward facilitating intracellular delivery and enhancement in the therapeutic efficacy of the molecular cargo. Toward this, an in-house synthesized porphyrin derivative, namely, 5-carboxymethyelene-oxyphenyl-10,15,20-tris(4-methoxyphenyl) porphyrin (UTriMA), was utilized for conjugation with the NLS sequence [PKKKRKV]. The three compounds synthesized during the course of the present work, namely DOTA-Lys-NLS, DOTA-UTriMA-Lys-NLS, and DOTA-Lys-UTriMA, were evaluated for cellular toxicity in cancer cell lines (HT1080), wherein all exhibited minimal dark toxicity. However, during photocytotoxicity studies with DOTA-Lys-UTriMA and DOTA-UTriMA-Lys-NLS conjugates in the same cell line, the latter exhibited significantly higher light-dependent toxicity compared to the former. Furthermore, the photocytotoxicity for DOTA-UTriMA-Lys-NLS in a healthy cell line (WI26VA4) was found to be significantly lower than that observed in the cancer cells. Fluorescence cell imaging studies carried out in HT1080 cancer cells revealed intracellular accumulation for the NLS-conjugated porphyrin (DOTA-UTriMA-Lys-NLS), whereas unconjugated porphyrin (DOTA-Lys-UTriMA) failed to do so. To evaluate the radiotherapeutic effects of the synthesized conjugates, all three compounds were radiolabeled with 177Lu, a well-known therapeutic radionuclide with high radiochemical purity (>95%). During in vitro studies, the [177Lu]Lu-DOTA-UTriMA-Lys-NLS complex exhibited the highest cell binding as well as internalization among the three radiolabeled complexes. Biological distribution studies for the radiolabeled compounds were performed in a fibrosarcoma-bearing small animal model, wherein significantly higher accumulation and prolonged retention of [177Lu]Lu-DOTA-UTriMA-Lys-NLS (9.32 ± 1.27% IA/g at 24 h p.i.) in the tumorous lesion compared to [177Lu]Lu-UTriMA-Lys-DOTA (2.3 ± 0.13% IA/g at 24 h p.i.) and [177Lu]Lu-DOTA-Lys-NLS complexes (0.26 ± 0.17% IA/g at 24 h p.i.) were observed. The results of the biodistribution studies were further corroborated by recording serial SPECT-CT images of fibrosarcoma-bearing Swiss mice administered with [177Lu]Lu-DOTA-UTriMA-Lys-NLS at different time points. Tumor regression studies performed with [177Lu]Lu-DOTA-UTriMA-Lys-NLS in the same animal model with two different doses [250 µCi (9.25 MBq) and 500 µCi (18.5 MBq)] resulted in a significant reduction in tumor mass in the treated group of animals. The above results revealed a definite enhancement in the targeting ability of molecular cargo upon conjugation with NLS and hence indicated that this strategy may be helpful for the preparation of drug-NLS conjugates as multimodal agents.

A Study of the Degree of Gall Bladder Wall Thickness and Its Impact on Patients Undergoing Laparoscopic Cholecystectomy.

Background The gold standard management for symptomatic gallstone disease is elective laparoscopic cholecystectomy, which has replaced open cholecystectomy. The wall thickness of the gallbladder is an indicator of cholecystitis in patients who have presented with symptoms of gallstone disease. The aim of this study was to evaluate preoperative gall bladder wall thickness by ultrasonography and assess its impact on the outcome of laparoscopic cholecystectomy, including conversion rate, complications, operative time, and postoperative hospital stay. Method This prospective study was conducted on 350 patients with symptomatic gallstone disease, those who had undergone laparoscopic cholecystectomy in Dr. Sampurnanand Medical College, Jodhpur, and attached hospitals from July 2019 to November 2021. On the basis of ultrasonography findings of gallbladder wall thickness, patients were divided into four groups: normal thickness - up to 2 mm, mild thickness - 3-4mm, moderate thickness - 5-6mm, and severe wall thickness - more than 6mm). Up to 2 millimeters thickness was considered as normal. Results The incidence of conversion rate, as well as intra or postoperative complications, were higher in moderate and severe wall thickness groups. The maximum incidence of complication rate is seen in moderately thickened group (33.33%). In severely thickened group, complication was seen in 100% of patients. Operative time, as well as postoperative hospital stay, were more in higher thickness groups. There was a statistically significant correlation between gallbladder wall thickness and conversion rate, complications operative time, and postoperative length of stay. Conclusion Increased gallbladder wall thickness causes increased intra as well as postoperative complications, more conversion to open procedure rate, increased operative time, and enhanced postoperative hospital stay. Among the total study population, 29.71% of patients had increased gallbladder wall thickness. In our study, a positive correlation was seen among gallbladder wall thickness, complication rate, conversion rate, intraoperative time, and postoperative hospital stay.

Institutional Analysis of the Surgical Outcomes of Cochlear Implantation in Deprived Population.

BACKGROUND: Cochlear implantation (CI) surgeries are safe and performed successfully in many patients; however, postoperative complications still occur, which may be influenced by socioeconomic and demographic variables.  Methodology: This is a retrospective observational study of 146 adults and children with hearing loss, who had CI surgery between 2017 and 2022. This study aims to assess the frequency and nature of surgical complications in patients from a low socioeconomic background who underwent CI surgery in different geographic areas. For the analysis of data, IBM SPSS Statistics for Windows, Version 21.0 (Released 2012; IBM Corp., Armonk, New York, United States) was used. RESULT: A total of 146 candidates were evaluated, out of which 82 were male (56.16%) and 64 (43.84%) were female. The age of patients at the time of surgery ranged from 1-50 years. All of the patients underwent unilateral CI. Eighteen implanted patients developed minor complications with an incidence rate of 12.31%. There were no major complications observed. Further, we did not observe any post-operative meningitis as our study group was vaccinated against pneumococcal and meningococcal diseases and Haemophilus influenzae type B (Hib). CONCLUSION: CI is an effective and safe surgical procedure for the treatment and rehabilitation of people who are deaf. It is possible to avoid complications by using meticulous surgical methods and regular post-operative monitoring to identify and treat any issues as soon as possible, regardless of socioeconomic status.

Evaluation of the effect of a cell penetrating peptide (TAT) towards tailoring the targeting efficacy and tumor uptake of porphyrin.

Cell penetrating peptides (CPPs) are known to possess a unique capacity to penetrate biological membranes and translocate various molecules into the cells. Therefore, porphyrin-CPP conjugates could be envisaged to boost the intracellular delivery of porphyrins thereby providing an improved tool for the development of agents for multi-modal applications for cancer management. Working in this direction, an unsymmetrically substituted porphyrin derivative was conjugated with a transactivating transcriptional activator peptide (TAT) and various in vitro and in vivo studies were carried out in order to study the effect of adding a CPP to the porphyrin derivative. MTT assay revealed the preferential light dependent toxicity of the porphyrin derivative which was further enhanced upon peptide conjugation. Fluorescence and flow cytometry studies revealed the relatively higher cellular internalization of the porphyrin-TAT conjugate in comparison with the porphyrin derivative. The elevated light dependent cell toxicity of the porphyrin-TAT conjugate along with its capability of generating cytotoxic singlet oxygen indicated the advantages of using the porphyrin-TAT conjugate for PDT applications. Also, porphyrin and the porphyrin-peptide conjugate were radiolabelled with 68Ga to investigate their possible potential as PET agents. In vivo biodistribution studies revealed a higher tumor uptake for the 68Ga-porphyrin-TAT conjugate (6.32 ± 1.24% IA per g) than for 68Ga-porphyrin (2.45 ± 0.88% IA per g) at 60 min post-administration. However, the observation of a higher non-target retention of the radiolabelled agents during in vivo studies might pose a limitation on their possible application in PET imaging.

Role of High-Sensitivity Troponin-T And N-Terminal Pro B-Type Natriuretic Peptide as an Early Predictor of Myocardial Dysfunction in Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Study.

Background: Acute cardiac complications are commonly seen in aneurysmal subarachnoid hemorrhage (aSAH) patients and may vary from subclinical electrocardiographic abnormalities, or reduced ejection fraction on echocardiography, elevated levels of cardiac markers (cardiac troponin and Brain natriuretic peptide) to heart failure. Objective: This study was done to evaluate the role of cardiac markers (high-sensitive Troponin-T and N-terminal pro-B-type natriuretic peptide) in early identification of cardiac complications and hence dysfunction. Methods: All consecutive patients with aSAH without any previous cardiac history were included. At admission, neurological evaluation using Hunt and Hess grading (H and H grade), with electrocardiography to look for any changes, echocardiography for ejection fraction, and any wall motion abnormalities was also done. The serial serum levels of high-sensitive Troponin-T (hsTnT) and N-terminal pro B-type natriuretic peptide (NT pro-BNP) for 7 consecutive days was measured with hsTnT >0.14 ng/ml and NT pro-BNP >150 pg/mL considered elevated. Results: A total of 69 patients were included. The elevated peak level of hsTnT and NT pro-BNP was seen in 55.1% and 69.6% of patients. A positive correlation was seen between hsTnT (P = 0.033) and NT pro-BNP (P = 0.011) and poor SAH grade (H and H grade 3-5), similarly, abnormal ECG also significantly correlated with elevated peak hsTnT (P = 0.002) and NT proBNP (P = 0.000). Also, significant difference in peak hsTnT (P = 0.000) and NT-proBNP (P = 0.000) in patients with or without reduced ejection fraction (EF). Conclusion: The elevated peak levels of hsTnT and NTproBNP along with ECG and echocardiography abnormalities may help in early identification of myocardial injury, hence cardiac dysfunction.

Treatment Dilemma of Latrogenic Pseudoaneurysm of the Intracavernous Internal Carotid Artery in Young Girl Following Transnasal Transsphenoidal Surgery: A Case Report.

Epistaxis following transnasal transsphenoidal (TNTS) removal of pituitary adenoma can be massive and life-threatening. The intracranial source of bleeding is usually the intracavernous segment of the internal carotid artery (ICA) or adjacent branches. Injury to the cavernous ICA can lead to pseudoaneurysm (PA) or fistula formation. Management of PA is different from saccular aneurysms. A timely diagnosis and adequate management can restore vessel integrity and prevent associated morbidity. A young patient of growth hormone-secreting pituitary adenoma, who underwent microscopic TNTS excision of the tumour, presented with massive epistaxis. Pseudoaneurysm of the cavernous ICA was initially not seen on computed tomography angiography and was later diagnosed on digital subtraction angiography. The attempted management of PA with coils without stent could not stop aneurysm recurrence. The management of such complicated PAs is discussed, and a literature review is done regarding epistaxis in growth hormone secreting adenoma.

Prospective Analysis of Role of hsTnT and NT-proBNP in Prediction of Neurogenic Stress Cardiomyopathy in Patients with Aneurysmal Subarachnoid Haemorrhage.

BACKGROUND: Neurogenic stress cardiomyopathy (NSC), also known as stress-induced cardiomyopathy (SIC), is a significant complication of aneurysmal subarachnoid hemorrhage and an important contributor to morbidity mortality. OBJECTIVE: This prospective observational study assessed whether the high sensitive troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NTproBNP) helps in the prediction of NSC after SAH. METHODS: The consecutive patients with aSAH without any cardiac history were included prospectively over 12 months. Neurological assessment for the grade of SAH (Hunt & Hess and WFNS grade), electrocardiogram, and echocardiography done at admission. The serial measurements of serum hsTnT and NTproBNP for consecutive 7 days done. The NSC is defined as transient hypokinesia of the ventricular wall on echocardiography. RESULTS: The study included 69 patients, and 7 (10.1%) were diagnosed with NSC. The NSC had a positive correlation with Hunt and Hess grade (P = 0.010), and the serum levels of hsTnT and NTproBNP were higher in patients with NSC in comparison to without NSC over all 7 days. The peak levels of hsTnT and NTproBNP were significantly higher in patients with cardiomyopathy (P = 0.000 and 0.032, respectively). The best cut-off level of peak hsTnT was 0.032 pg/dl to predict cardiomyopathy with sensitivity and specificity of 100% and 80%, respectively, and NTproBNP was 430.6 ng/dL with sensitivity and specificity of 86% and 73%, respectively. CONCLUSION: The peak levels of hsTnT and NTproBNP with abnormal ECG and echocardiography at admission help identify NSC in the early phase of aSAH.

Quadrupled Hamstring Graft Diameter Adequacy in Anterior Cruciate Ligament Reconstruction Using Patient Anthropometry: A Prospective Cohort Study in Indian Males.

Background and aim The diameter of the graft used for the reconstruction of the anterior cruciate ligament (ACL) is an important determinant for the overall strength and future outcome of the operative procedure. Preoperative prediction of quadrupled hamstrings autograft (QHAG) diameter can prove to be of help in forecasting the need for augmentation or alternative grafts like quadriceps, bone-patellar tendon-bone autograft, and synthetic grafts. The relationship between the preoperatively assessed anthropometric parameters and the obtained quadrupled hamstrings graft diameter has not been extensively studied, especially in the population of Indian origin. This study aimed at investigating whether a correlation exists between the measured anthropometric parameters like age, weight, height, thigh circumference, and body mass index (BMI) and the intraoperatively obtained diameter of hamstring graft for ACL reconstruction in the study population of Indian male subjects. Study design A prospective cohort study conducted in a tertiary care center and teaching hospital in a district in central Uttar Pradesh, India. Methods The preoperative anthropometric data (age, height, weight, BMI, and thigh circumference of the injured side) of 73 Indian male subjects undergoing primary ACL reconstructive surgeries between May 2018 and August 2020 were prospectively collected, and their respective intraoperative QHAG diameters measured and recorded. Pearson's correlation test was employed to determine the correlation between the preoperative demographic and anthropometric data and the obtained corresponding graft diameters. Simple linear regression was performed to obtain the graphical plots and determine the relationship between the dependent and independent variables. Of these, the variables showing significant association were subjected to stepwise linear regression to identify and exclude the confounder(s) and obtain the predicted equation. Results The study comprised 73 male participants. The study participants' mean age was found to be 33.7 years, mean height was 173.1 cm, mean weight was 71.2 kg, mean BMI was 23.7 kg/m2, mean thigh circumference was 50.4 cm, and the obtained mean graft diameter was 8.0 mm. A strongly positive correlation was observed between height and the graft diameter (r=0.940, P=0.000) and thigh circumference and the graft diameter (r=0.769, P=0.000). In contrast, weight showed a moderately positive correlation with the graft diameter (r=0.514, P=0.000). A very weakly positive correlation was observed between the BMI of the subjects and the obtained graft diameters (r=0.236, P=0.045). However, no correlation was observed between the age and the final graft diameters (r=0.140, P=0.238). Subsequent linear regression analysis indicates that only height (R2=0.883, P=0.000; strong) and the thigh circumference (R2=0.591, P=0.000; moderate) share a significant predictive value for the obtained QHAG. Both height and thigh circumference together were good predictors for graft diameter as determined by multiple regression (F (2,70)=272.372, P<0.001), with an R2 of 0.886. Conclusion Certain anthropometric parameters depict a positive correlation with the QHAG diameter and can assist in preoperative planning, predicting the possible harvested graft diameter and the need for alternative grafts or augmentation during ACL reconstructive surgeries.

Simultaneous knockout of multiple LHCF genes using single sgRNAs and engineering of a high-fidelity Cas9 for precise genome editing in marine algae.

The CRISPR/Cas9 system is an RNA-guided sequence-specific genome editing tool, which has been adopted for single or multiple gene editing in a wide range of organisms. When working with gene families with functional redundancy, knocking out multiple genes within the same family may be required to generate a phenotype. In this study, we tested the possibility of exploiting the known tolerance of Cas9 for mismatches between the single-guide RNA (sgRNA) and target site to simultaneously introduce indels in multiple homologous genes in the marine diatom Phaeodactylum tricornutum. As a proof of concept, we designed two sgRNAs that could potentially target the same six light-harvesting complex (LHC) genes belonging to the LHCF subgroup. Mutations in up to five genes were achieved simultaneously using a previously established CRISPR/Cas9 system for P. tricornutum. A visible colour change was observed in knockout mutants with multiple LHCF lesions. A combination of pigment, LHCF protein and growth analyses was used to further investigate the phenotypic differences between the multiple LHCF mutants and WT. Furthermore, we used the two same sgRNAs in combination with a variant of the existing Cas9 where four amino acids substitutions had been introduced that previously have been shown to increase Cas9 specificity. A significant reduction of off-target editing events was observed, indicating that the altered Cas9 functioned as a high-fidelity (HiFi) Cas9 nuclease.

Catalytic level identification of ZSM-5 on biomass pyrolysis and aromatic hydrocarbon formation.

Zeolite socony mobil-5 (ZSM-5) is a common catalyst used for biomass pyrolysis. Nevertheless, the quantitative information on the catalytic behavior of ZSM-5 on biomass pyrolysis is absent so far. This study focuses on the catalytic pyrolysis phenomena and mechanisms of biomass wastes using ZSM-5 via thermogravimetric analyzer and pyrolysis-gas chromatography/mass spectrometry, with particular emphasis on catalytic level identification and aromatic hydrocarbons (AHs) formation. Two biomass wastes of sawdust and sorghum distillery residue (SDR) are investigated, while four biomass-to-catalyst ratios are considered. The analysis suggests that biomass waste pyrolysis processes can be divided into three zones, proceeding from a heat-transfer dominant zone (zone 1) to catalysis dominant zones (zones 2 and 3). The indicators of the intensity of difference (IOD), catalytic effective area, catalytic index (CI), and aromatic enhancement index are conducted to measure the catalytic effect of ZSM-5 on biomass waste pyrolysis and AHs formation. The maximum IOD occurs in zone 2, showing the highest intensity of the catalytic effect. The CI values of the two biomass wastes increase with increasing the biomass-to-catalyst ratio. However, there exists a threshold for sawdust pyrolysis, indicating a limit for the catalytic effect on sawdust. The higher the catalyst addition, the higher the AHs proportion in the vapor stream. When the biomass-to-catalyst ratio is 1/10, AHs formation is intensified significantly, especially for sawdust. Overall, the indexes conducted in the present study can provide useful measures to identify the catalytic pyrolysis dynamics and levels.

Pancreatic Injury in COVID-19 Patients.

BACKGROUND AND AIM: Coronavirus disease 2019 (COVID 2019) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause multisystem dysfunction. We studied pancreatic injury (serum amylase and serum lipase levels) in COVID-19 patients. METHODS: A retrospective study involving 42 COVID-19 patients (diagnosed by real-time PCR) admitted to a tertiary care hospital was conducted. Serum amylase and serum lipase levels were analysed in relation to severity of COVID-19 and mortality. RESULTS: Mean age of patients was 50 ± 16 years, with male to female ratio of 3.7:1. Serum amylase was elevated in 14 patients (33%). Serum lipase was elevated in 7 out of 29 patients (24.1%). Mortality was seen in 18 patients (42.8%). Serum amylase or lipase did not correlate with severity of COVID-19 or its mortality. However, both patients who had high lipase (>3times) died. CONCLUSION: The prevalence of hyperamylasemia in patients of COVID-19 was 33%, while that of elevated lipase was 24.1%. Pancreatic injury failed to show any statistically significant relation to severity or outcome of COVID-19.

Biochemical, thermodynamic and structural characteristics of a biotechnologically compatible alkaline protease from a haloalkaliphilic, Nocardiopsis dassonvillei OK-18.

This report describes purification strategies, biochemical properties and thermodynamic analysis of an alkaline serine protease from a marine actinomycete, Nocardiopsis dassonvillei strain OK-18. The solvent tolerance, broad thermal-pH stability, favourable kinetics and thermodynamics suggest stability of the enzymatic reaction. The enzyme was active in the range of pH 7-12 and 37-90 °C, optimally at pH 9 and 70 °C. The deactivation rate constant (Kd), half-life (t½), enthalpy (ΔH*), entropy (ΔS*), activation energy (E) and change in free energy (ΔG*) suggested stability and spontaneity of the reaction. ß-Sheets as revealed by the Circular dichroism (CD) spectroscopy, were the major elements in the secondary structure of the enzyme, while Fourier-transform infrared spectroscopy (FTIR) indicated the presence of amide I and amide II. Based on the liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF-MS) analysis, the amino acid sequence had only 38% similarity with other proteases of Nocardiopsis strains, suggesting its novelty. The Ramachandran Plot revealed the location of the amino acid residues in the most favored region. The blood de-staining, gelatin hydrolysis, silver recovery and deproteinization of crab shells established the biotechnological potential of the enzyme.

Pre-Clinical Testing of Microwave Radiometer and a Pilot Study on the Screening Inflammation of Knee Joints.

This article presents the pre-clinical evaluation of our custom-built, single-band microwave radiometer centered at 1.3 GHz for deep tissue thermometry, and a pilot study on volunteers for passive detection of inflammation in knee joints. The electromagnetic (EM) compatibility of the battery-operated radiometer for clinical use was assessed as per International Special Committee on Radio Interference (CISPR) 22 standard. The ability to detect inflammation in knee joints was assessed using a substrate integrated waveguide antenna connected to the radiometer. EM compatibility tests carried out in the laboratory indicated device immunity to intentional radiated interference up to -20 dBm injected power in the global system for mobile communication frequency band, and pre-compliance to CISPR 22 standard. Radiometer temperature measurements recorded at the lateral and medial aspects of both knees of 41 volunteers indicated mean temperature greater than 33°C for the diseased sites compared with the mean temperature of 28°C measured for the healthy sites. One-way analysis of variance statistics indicated significantly (P < 0.005) higher radiometer temperature at the diseased sites unlike the healthy sites. Thus, the EM pre-compliance of the device and the potential to measure deep tissue inflammation were demonstrated. Bioelectromagnetics. 2019;40:402-411. © 2019 Bioelectromagnetics Society.

Dystextia and dystypia as modern stroke symptoms: A case series and literature review.

Stroke recognition remains a barrier to care in cerebrovascular disease. Despite an increasing reliance on digital communication, the clinical utility of deficits relating to technology remains unexplored. Dystextia and dystypia, terms used to refer to impairments in texting and typing, respectively, may serve as modern indicators of stroke and provide information regarding stroke duration, symptomatology, and etiological diagnosis. In this report, we describe two cases in which dystextia and dystypia were involved in stroke presentation and perform a literature review surrounding these signs. Four out of six cases identified on literature review in which stroke etiology was described, in addition to both of our presented cases, were found to be embolic in origin. While shared lesion topography involving the left posterior upper insular cortex and superior longitudinal fasciculus was identified in our cases, additional research is required for proper symptom-lesion mapping. Further characterization of dystextia and dystypia, and their corresponding localization, may assist in stroke diagnosis and guide investigations.

Haloperidol-induced parkinsonism is attenuated by varenicline in mice.

Background Parkinson's disease (PD) is a neurodegenerative disorder of the central nervous system (CNS). However, there is no known drug to stop/slow down this neurodegeneration. Varenicline is an anti-smoking drug and has the potential to prevent neurodegeneration. Thus, the present study was designed to evaluate the effect of varenicline in animal models of PD. Methods Levodopa and haloperidol were administered in doses of 30 and 1 mg/kg, intraperitoneally (i.p.), respectively. Group 1 was administered haloperidol; groups 2, 3 and 4 were administered haloperidol along with varenicline in doses of 0.5, 1.5 and 2.5 mg/kg, i.p., respectively and group 5 was administered levodopa along with haloperidol. Varenicline was administered daily, 30 min prior to the administration of haloperidol. Varenicline was administered for the first 8 days, and then from the 9th day until the 15th day. Behavioral assessment (rotarod and catalepsy tests) was performed on days 9 and 15. Assessment of striatal dopamine levels and histopathology were also performed. Results In the haloperidol-treated groups, significant decrease in latency to fall off (on rotarod) and increase in catalepsy duration (in catalepsy test) were observed as compared to the control group. In the levodopa-treated group, significant increase in latency to fall off the rotarod and significant decrease in catalepsy duration were observed as compared to the haloperidol-treated groups. Further, on day 9, varenicline (2.5 mg/kg) significantly increased the latency to fall off the rotarod, while varenicline (0.5 and 1.5 mg/kg) did not cause any significant change in latency to fall off the rotarod as compared to the haloperidol-treated group. On day 15, significant increase in latency to fall off the rotarod was observed in varenicline (at all doses) as compared to the haloperidol-treated group. In the catalepsy test, the varenicline-treated (at all doses) groups showed significant decrease in duration of catalepsy on day 9 and day 15 as compared to the haloperidol-treated group. Significant decrease in striatal dopamine levels was observed among the haloperidol-treated groups as compared to the control group. Further, varenicline-treated (at all doses) and levodopa-treated groups showed significant increase in striatal dopamine levels when compared with the haloperidol-treated group. In histology, varenicline (0.5 mg/kg) showed moderate decrease in neurons, while varenicline (1.5 and 2.5 mg/kg) showed mild decrease in neurons. However, the levodopa-treated group did not show any significant decrease in neurons. Thus, varenicline has shown promising results and has provided novel strategy for the treatment of PD.

Do Lordotic Cages Provide Better Segmental Lordosis Versus Nonlordotic Cages in Lateral Lumbar Interbody Fusion (LLIF)?

STUDY DESIGN: A retrospective comparative radiographic review. OBJECTIVE: To evaluate the radiographic changes brought about by lordotic and nonlordotic cages on segmental and regional lumbar sagittal alignment and disk height in lateral lumbar interbody fusion (LLIF). SUMMARY OF BACKGROUND DATA: The effects of cage design on operative level segmental lordosis in posterior interbody fusion procedures have been reported. However, there are no studies comparing the effect of sagittal implant geometry in LLIF. METHODS: This is a comparative radiographic analysis of consecutive LLIF procedures performed with use of lordotic and nonlordotic interbody cages. Forty patients (61 levels) underwent LLIF. Average age was 57 years (range, 30-83 y). Ten-degree lordotic PEEK cages were used at 31 lumbar interbody levels, and nonlordotic cages were used at 30 levels. The following parameters were measured on preoperative and postoperative radiographs: segmental lordosis; anterior and posterior disk heights at operative level; segmental lordosis at supra-level and subjacent level; and overall lumbar (L1-S1) lordosis. Measurement changes for each cage group were compared using paired t test analysis. RESULTS: The use of lordotic cages in LLIF resulted in a significant increase in lordosis at operative levels (2.8 degrees; P=0.01), whereas nonlordotic cages did not (0.6 degrees; P=0.71) when compared with preoperative segmental lordosis. Anterior and posterior disk heights were significantly increased in both groups (P<0.01). Neither cage group showed significant change in overall lumbar lordosis (lordotic P=0.86 vs. nonlordotic P=0.25). CONCLUSIONS: Lordotic cages provided significant increase in operative level segmental lordosis compared with nonlordotic cages although overall lumbar lordosis remained unchanged. Anterior and posterior disk heights were significantly increased by both cages, providing basis for indirect spinal decompression.

Comparison of fluoxetine and 1-methyl-L-tryptophan in treatment of depression-like illness in Bacillus Calmette-Guerin-induced inflammatory model of depression in mice.

BACKGROUND: The inflammatory response system has been implicated in the pathophysiology of major depression. The pro-inflammatory cytokines like interferon-γ induce the enzyme indoleamine-2,3-dioxygenase (IDO) of the kynurenine pathway of tryptophan metabolism. The induction of IDO reduces the availability of tryptophan for serotonin synthesis. Furthermore, the metabolites of kynurenine pathway have neurotoxic property, which along with decreased serotonin may account for depression-like illness. METHODS: The aim of this study was to compare the effects of treatment with fluoxetine and 1-methyl-L-tryptophan (1-MT) on Bacillus Calmette-Guerin (BCG)-induced inflammatory model of depression in mice. Behavioral tests included locomotor activity, forced swim test (FST) and tail suspension test (TST). Oxidative stress was assessed by examining the levels of thiobarbituric acid reactive species (TBARS) and non-protein thiols (NP-SH) in homogenized whole brain samples. Comet assays were performed to assess neurotoxicity. RESULTS: The results of this study demonstrate that BCG treatment resulted in an increase in duration of immobility in FST and TST as compared to the saline group. Further, it produced a significant increase in the brain TBARS levels and decrease in the brain NP-SH levels. The hippocampal tissue from BCG group had significantly more comet cells than the saline group. 1-MT and fluoxetine were able to reverse the BCG-induced depression-like behavior and the derangement in oxidative stress parameters. Fluoxetine and 1-MT also reversed the BCG-induced neurotoxicity in such mice. CONCLUSIONS: 1-Methyl-L-tryptophan exhibits antidepressant-like effect comparable to that of fluoxetine in treating BCG-induced depression-like behavior in mice.

Effect of amino acids on the repression of alkaline protease synthesis in haloalkaliphilic Nocardiopsis dassonvillei.

A newly isolated salt-tolerant alkaliphilic actinomycete, Nocardiopsis dassonvillei strain OK-18 grows on mineral salts medium with glucose as carbon source. It also grows and produces protease with amino acids as sole carbon source. The synthesis of extracellular alkaline protease parallel to growth was repressible by substrate concentrations. The absolute production of the protease was delinked with growth under nutritional stress, as protease production was high, despite poor growth. When amino acids served as the sole source of carbon and nitrogen, the enzyme production was significantly controlled by the number of amino acids. Maximal protease production was achieved with proline, asparagine, tyrosine, alanine, methionine and valine as sole source of carbon and nitrogen in minimal medium. With the increasing number of different amino acids in the presence and absence of glucose, the protease production was synergistically lower as compared to complex medium.