Color Doppler Ultrasound Indices as Predictors of Propranolol Response in Infantile Hemangioma: A Prospective Study.

OBJECTIVE: To evaluate the utility of color Doppler ultrasonography in assessing infantile hemangioma response to treatment with oral propranolol. METHODS: A prospective study was conducted between January, 2016 and December, 2022, wherein children with symptomatic (ulceration, bleeding, pain and scarring) infantile hemangioma were given oral propranol (2 mg/kg per day in three divided doses) as outpatient therapy. The clinical response was assessed three months post-initiation of treatment (intermediate clinical response) and three months post-completion of treatment (final clinical response, FCR). The primary outcome measurement was a clinical and radiological response (resistivity index (RI), pulsatility index (PI) and peak systolic velocity) to treatment. The secondary outcomes assessed were the complications related to treatment. RESULTS: Out of 601 patients who were started on propranolol, 99 developed severe adverse effects and were excluded from analysis. At FCR assessment, out of 502 participants, 64.3% (n = 323) showed excellent response, 17.7% (n = 89) showed partial, and 17.9% (n = 90) were non-responders. A significant increase in RI and PI values was noted in all children following propranolol treatment for six months. An increase > 7.5% in RI could identify responders with 92% sensitivity, 91% specificity and area under the curve (AUC) of 0.963. An increase of > 11.5% in PI could identify responders with 86% sensitivity, 91% specificity and AUC of 0.896. Patients initially showing no response but later becoming excellent responders had significantly higher RI and PI values. CONCLUSIONS: Color Doppler ultrasonography is a valuable tool in predicting the treatment outcome of infantile hemangioma using propranolol.

Efficacy of Individualized Homeopathic Medicines in the Treatment of Hemorrhoids: Double-Blind, Randomized, Placebo-Controlled Trial.

Objectives: To investigate the efficacy and safety of individualized homeopathic medicines (IHMs) in treating hemorrhoids compared with placebo. Design: This is a double-blind, randomized (1:1), two parallel arms, placebo-controlled trial. Setting: The trial was conducted at the surgery outpatient department of the State National Homoeopathic Medical College and Hospital, Lucknow, Uttar Pradesh, India. Subjects: Patients were 140 women and men, aged between 18 and 65 years, with a diagnosis of primary hemorrhoids grades I-III for at least 3 months. Excluded were the patients with grade IV hemorrhoids, anal fissure, and fistula, hypertrophic anal papillae, inflammatory bowel disease, coagulation disorders, rectal malignancies, obstructed portal circulation, patients requiring immediate surgical intervention, and vulnerable samples. Interventions: Patients were randomized to Group 1 (n = 70; IHMs plus concomitant care; verum) and Group 2 (n = 70; placebos plus concomitant care; control). Outcome measures: Primary-the anorectal symptom severity and quality-of-life (ARSSQoL) questionnaire, and secondary-the EuroQol 5-dimensions 5-levels (EQ-5D-5L) questionnaire and EQ visual analogue scale (VAS); all of them were measured at baseline, and every month, up to 3 months. Results: Out of the 140 randomized patients, 122 were protocol compliant. Intention-to-treat sample (n = 140) was analyzed. The level of significance was set at p < 0.05 two tailed. Statistically significant between-group differences were elicited in the ARSSQoL total (Mann-Whitney U [MWU]: 1227.0, p < 0.001) and EQ-5D-5L VAS (MWU: 1228.0, p = 0.001) favoring homeopathy against placebos. Sulfur was the most frequently prescribed medicine. No harm or serious adverse events were reported from either of the groups. Conclusions: IHMs demonstrated superior results over placebo in the short-term treatment of hemorrhoids of grades I-III. The findings are promising, but need to be substantiated by further phase 3 trials. Clinical Trial Registration Number: CTRI/2020/03/024342.

Polyubiquitin protein of Aedes aegypti as an interacting partner of dengue virus envelope protein.

Dengue virus (DENV) is an arbovirus that comprises four antigenically different serotypes. Aedes aegypti (Diptera: Culicidae) acts as the principal vector for DENV transmission, and vector control is crucial for dengue fever epidemic management. To design effective vector control strategies, a comprehensive understanding of the insect vector and virus interaction is required. Female Ae. aegypti ingests DENV during the acquisition of a blood meal from an infected human. DENV enters the insect midgut, replicates inside it and reaches the salivary gland for transmitting DENV to healthy humans during the subsequent feeding cycles. DENV must interact with the proteins present in the midgut and salivary glands to gain entry and accomplish successful replication and transmission. Ae. aegypti midgut cDNA library was prepared, and yeast two-hybrid screening was performed against the envelope protein domain III (EDIII) protein of DENV-2. The polyubiquitin protein was selected from the various candidate proteins for subsequent analysis. Polyubiquitin gene was amplified, and the protein was purified in a heterologous expression system for in vitro interaction studies. In vitro pull-down assay presented a clear interaction between polyubiquitin protein and EDIII. To further confirm this interaction, a dot blot assay was employed, and polyubiquitin protein was found to interact with DENV particles. Our results enable us to suggest that polyubiquitin plays an important role in DENV infection within mosquitoes.

Evaluating Ayurvedic mouthwash and soda-salt mouthwash for oral mucositis in head and neck cancer: A randomized controlled trial.

BACKGROUND: Patients undergoing radiotherapy (RT) or concurrent chemo-radiation (CCRT) for head and neck squamous cell carcinoma (HNSCC) often suffer from side effects such as mucositis, xerostomia, pharyngitis, laryngitis, and pain, which are being managed symptomatically by alcohol-based mouthwashes. OBJECTIVES: To determine the effectiveness of Ayurvedic mouthwash "Draksha Guduchyadi Kashaya" in reducing the severity of oral side effects of chemo-radiation. MATERIAL AND METHODS: This concurrent parallel randomized controlled study was conducted at Sir Sunderlal Hospital, BHU, on 70 HNSCC patients scheduled to undergo RT/CCRT. Patients who met the inclusion-exclusion criteria were enrolled, and 35 were randomly assigned to either the intervention group (Ayurveda) or the control group using a simple random technique (lottery method). Blinding was not implemented in this study. Patients in the intervention group (Ayurveda) were instructed to perform kavala with 50 ml of "Draksha Guduchyadi Kashaya" for 2 min, ten times daily, while the control group performed 2-min gargling with soda-salt mouthwash ten times daily. RESULTS: Out of the 70 patients enrolled, data from 60 patients were analyzed, revealing statistically significant differences in the onset of mucositis (p = 0.049), pharyngitis (p = 0.034), laryngitis (p = 0.009) and intensity of variables such as mucositis (p = 0.000), xerostomia (p = 0.046), pharyngitis (p = 0.002), laryngitis (p = 0.035), and pain (p = 0.000). These findings indicate that Ayurvedic mouthwash may be beneficial in managing the oral side effects of chemo-radiation in HNSCC. CONCLUSION: This AYUSH financially supported trial (Reg No: CTRI/2020/04/024672) demonstrates promise as a safe and cost-effective alternative for managing oral complications of RT/CCRT, offering complementary treatment for comprehensive cancer care.

The healing potential of Draksha-guduchyadi kavala in radiotherapy induced oral mucositis in non-metastatic squamous cell carcinoma of head and neck: A comparative case study.

Patients undergoing Radiotherapy (RT) for Head and Neck carcinoma often suffer from side effects such as mucositis, xerostomia, pharyngitis, laryngitis and pain which are being managed symptomatically by mouthwashes of soda-salt, chlorhexidine or betadine. Among the side effects, oral mucositis is the most debilitating one. This comparative case study comprises of 4 patients undergoing RT. Here, 2 patients each are randomly allocated into two groups. One group received the existing prophylactic management i.e., Sodium bicarbonate-salt solution mouth wash and the other group received, Draksha-guduchyadi yoga for kavala (gargling). Both the sets of patients were asked to perform gargling, from the first day of radiation to 15 days thereafter. The effectiveness of both mouthwashes was compared for their healing potential on oral mucositis by RTOG grading. The reduction in mucositis was significant in the group which received Ayurvedic mouthwash compared to the other group. This study positively highlights the contribution of Ayurveda in cancer treatment especially in the field of quality of life.

Utility of Blood as the Clinical Specimen for the Molecular Diagnosis of Post-Kala-Azar Dermal Leishmaniasis.

The countries in the Indian subcontinent have reported a dramatic decline in visceral leishmaniasis (VL) cases. However, the presence of the parasite reservoir in the form of post-kala-azar dermal leishmaniasis (PKDL), a dermal sequel of VL, is a hurdle in attaining VL elimination. Presently employed clinical specimens for the diagnosis of PKDL include skin biopsy specimens and slit skin smears. In this study, the use of blood as a clinical specimen was investigated in different manifestations of PKDL in India. This is a bicentric study (National Institute of Pathology, Indian Council of Medical Research [ICMR], New Delhi, and Institute of Medical Sciences [IMS], Banaras Hindu University, Varanasi), with 215 participants (120 PKDL patients and 95 controls). Highly sensitive quantitative real-time PCR (Q-PCR) and field-deployable loop-mediated isothermal amplification (LAMP) were employed using blood samples for diagnosis. Promising sensitivities of 77.50% (95% confidence interval [CI], 69.24 to 84.05%) for Q-PCR and 70.83% (95% CI, 62.16 to 78.22%) for LAMP were obtained for the diagnosis of PKDL. Further, enhanced sensitivities of 83.33% (95% CI, 71.28 to 90.98%) and 77.78% (95% CI, 65.06 to 86.80%) for Q-PCR and LAMP, respectively, were recorded for the detection of macular cases. The study revealed an inverse correlation between the parasite load estimated in slit and blood samples, thereby favoring the use of blood for the diagnosis of the macular variant, which may be missed due to scant parasite loads in the slit. This study is the first to propose the promising potential of blood as a clinical specimen for accurate diagnosis of PKDL, which would aid in fast-tracking VL elimination.

IFN-γ+ CD4+T cell-driven prophylactic potential of recombinant LDBPK_252400 hypothetical protein of Leishmania donovani against visceral leishmaniasis.

Visceral leishmaniasis (VL) is a potentially fatal parasitic disease causing high morbidity and mortality in developing countries. Vaccination is considered the most effective and powerful tool for blocking transmission and control of diseases. However, no vaccine is available so far in the market for humans. In the present study, we characterized the hypothetical protein LDBPK_252400 of Leishmania donovani (LdHyP) and explored its prophylactic behavior as a potential vaccine candidate against VL. We found reduced hepato-splenomegaly along with more than 50% parasite reduction in spleen and liver after vaccination in mice. Protection in vaccinated mice after the antigen challenge correlated with the stimulation of antigen specific IFN-γ expressing CD4+T cell (~4.6 fold) and CD8+T cells (~2.1 fold) in vaccinated mice in compared to infected mice, even after 2-3 months of immunization. Importantly, antigen-mediated humoral immunity correlated with high antigen specific IgG2/IgG1 responses in vaccinated mice. In vitro re-stimulation of splenocytes with LdHyP enhances the expression of TNF-α, IFN-γ, IL-12 and IL-10 cytokines along with lower IL-4 cytokine and IL-10/IFN-γ ratio in vaccinated mice. Importantly, we observed ~3.5 fold high NO production through activated macrophages validates antigen mediated cellular immunity induction, which is critical in controlling infection progression. These findings suggest that immunization with LdHyP mount a very robust immunity (from IL-10 towards TFN-γ mediated responses) against L. donovani infection and could be explored further as a putative vaccine candidate against VL.

Anti-Interleukin-10 Unleashes Transcriptional Response to Leishmanial Antigens in Visceral Leishmaniasis Patients.

Visceral leishmaniasis (VL; Leishmania donovani) cases produce interferon-γ and tumor necrosis factor in response to soluble leishmanial antigen (SLA) in whole-blood assays. Using transcriptional profiling, we demonstrate the impact of interleukin-10 (IL-10), a cytokine implicated in VL, on this response. SLA stimulation identified 28 differentially expressed genes (DEGs), 17/28 in a single network with TNF as hub. SLA plus anti-IL-10 produced 454 DEGs, 292 in a single network with TNF, IFNG, NFKBIA, IL6, and IL1B as hubs in concert with a remarkable chemokine/cytokine storm. Our data demonstrate the singular effect of IL-10 as a potent immune modulator in VL.

The NK cell granule protein NKG7 regulates cytotoxic granule exocytosis and inflammation.

Immune-modulating therapies have revolutionized the treatment of chronic diseases, particularly cancer. However, their success is restricted and there is a need to identify new therapeutic targets. Here, we show that natural killer cell granule protein 7 (NKG7) is a regulator of lymphocyte granule exocytosis and downstream inflammation in a broad range of diseases. NKG7 expressed by CD4+ and CD8+ T cells played key roles in promoting inflammation during visceral leishmaniasis and malaria-two important parasitic diseases. Additionally, NKG7 expressed by natural killer cells was critical for controlling cancer initiation, growth and metastasis. NKG7 function in natural killer and CD8+ T cells was linked with their ability to regulate the translocation of CD107a to the cell surface and kill cellular targets, while NKG7 also had a major impact on CD4+ T cell activation following infection. Thus, we report a novel therapeutic target expressed on a range of immune cells with functions in different immune responses.

Type I Interferons Suppress Anti-parasitic Immunity and Can Be Targeted to Improve Treatment of Visceral Leishmaniasis.

Type I interferons (IFNs) play critical roles in anti-viral and anti-tumor immunity. However, they also suppress protective immune responses in some infectious diseases. Here, we identify type I IFNs as major upstream regulators of CD4+ T cells from visceral leishmaniasis (VL) patients. Furthermore, we report that mice deficient in type I IFN signaling have significantly improved control of Leishmania donovani, a causative agent of human VL, associated with enhanced IFNγ but reduced IL-10 production by parasite-specific CD4+ T cells. Importantly, we identify a small-molecule inhibitor that can be used to block type I IFN signaling during established infection and acts synergistically with conventional anti-parasitic drugs to improve parasite clearance and enhance anti-parasitic CD4+ T cell responses in mice and humans. Thus, manipulation of type I IFN signaling is a promising strategy for improving disease outcome in VL patients.

Refining wet lab experiments with in silico searches: A rational quest for diagnostic peptides in visceral leishmaniasis.

BACKGROUND: The search for diagnostic biomarkers has been profiting from a growing number of high quality sequenced genomes and freely available bioinformatic tools. These can be combined with wet lab experiments for a rational search. Improved, point-of-care diagnostic tests for visceral leishmaniasis (VL), early case detection and surveillance are required. Previous investigations demonstrated the potential of IgG1 as a biomarker for monitoring clinical status in rapid diagnostic tests (RDTs), although using a crude lysate antigen (CLA) as capturing antigen. Replacing the CLA by specific antigens would lead to more robust RDTs. METHODOLOGY: Immunoblots revealed L. donovani protein bands detected by IgG1 from VL patients. Upon confident identification of these antigens by mass spectrometry (MS), we searched for evidence of constitutive protein expression and presence of antigenic domains or high accessibility to B-cells. Selected candidates had their linear epitopes mapped with in silico algorithms. Multiple high-scoring predicted epitopes from the shortlisted proteins were screened in peptide arrays. The most promising candidate was tested in RDT prototypes using VL and nonendemic healthy control (NEHC) patient sera. RESULTS: Over 90% of the proteins identified from the immunoblots did not satisfy the selection criteria and were excluded from the downstream epitope mapping. Screening of predicted epitope peptides from the shortlisted proteins identified the most reactive, for which the sensitivity for IgG1 was 84% (95% CI 60-97%) with Sudanese VL sera on RDT prototypes. None of the sera from NEHCs were positive. CONCLUSION: We employed in silico searches to reduce drastically the output of wet lab experiments, focusing on promising candidates containing selected protein features. By predicting epitopes in silico we screened a large number of peptides using arrays, identifying the most promising one, for which IgG1 sensitivity and specificity, with limited sample size, supported this proof of concept strategy for diagnostics discovery, which can be applied to the development of more robust IgG1 RDTs for monitoring clinical status in VL.

Abnormal B-Cell Subset and Blimp-1-Mediated Humoral Responses Associated With Visceral Leishmaniasis Pathogenesis.

B-cells have a spectrum of functions ranging from antibody production to antigen presentation and have additional vital roles in immune mechanisms. There is rudimentary knowledge about the role of B-cells in intracellular infections with contradictory findings. We explored the role of B-cell dysfunctions in visceral leishmaniasis (VL) pathogenesis in terms of the phenotypic and functional properties of B-cells during the course of disease. This study was performed on blood and splenic aspirates (SA) of VL cases pre- and post-treatment. Whole blood was used for flow cytometric studies for determining the profiles of B-cells at different time-points of treatment. Peripheral blood mononuclear cells were used for magnetic purification of B-cells, for transcriptional studies by real-time polymerase chain reaction (RT-PCR). Serum/plasma was used for direct agglutination test for determining parasite-specific antibodies and SA were used for scoring the presence of parasite by microscopic examination. Flow cytometric studies depicted decreased B-cell percentages during the entire course of disease and attainment of exhaustive phenotype with tissue-like memory cell markers, indicative of B-cell dysfunctions in VL. In addition, B-cells had compromised abilities of antigen processing and presentation and altered levels of B-lymphocyte-induced maturation protein-1 (Blimp-1). Blimp-1 expression goes hand in hand with B-cell maturation antigen and transmembrane activator and calcium modulator (TACI) and cyclophilin ligand interactor, suggestive of its role in promoting plasma cell survival and antibody production. Elevated level of VL-specific antibody titre was directly correlated with exhausted phenotype and also with disease severity during VL. This study indicated for impaired B-cell functions during chronic infection which may lead to pathological consequences in human VL.

Indian guidelines on neurosurgical interventions in psychiatric disorders.

Neurosurgery for psychiatric disorders (NPD) has been practiced for >80 years. However, the interests have waxed and waned, from 1000s of surgeries in 1940-1950s to handful of surgery in 60-80s. This changed with the application of deep brain stimulation surgery, a surgery, considered to be "reversible" there has been a resurgence in interest. The Indian society for stereotactic and functional neurosurgery (ISSFN) and the world society for stereotactic and functional neurosurgery took the note of the past experiences and decided to form the guidelines for NPD. In 2011, an international task force was formed to develop the guidelines, which got published in 2013. In 2018, eminent psychiatrists from India, functional neurosurgeon representing The Neuromodulation Society and ISSFN came-together to deliberate on the current status, need, and legal aspects of NPD. In May 2018, Mental Health Act also came in to force in India, which had laid down the requirements to be fulfilled for NPD. In light of this after taking inputs from all stakeholders and review of the literature, the group has proposed the guidelines for NPD that can help to steer these surgery and its progress in India.

Identifying the Factors Causing Delayed Presentation of Cancer Patients to a Government Medical College of Central India.

BACKGROUND: The incidence of cancer is increasing throughout the world. One of the prime aims of its management is early diagnosis and therapeutic intervention. Factors causing delay to either of these goals should be identified and rectified. AIM: To identify the factors causing delayed initial diagnosis and subsequent management in patients presenting to the Oncology department. MATERIALS AND METHODS: Three hundred proven cancer patients were prospectively evaluated for the pattern of presentation to the outpatient Department of Radiation Oncology of a Government Medical College (MC) in Central India. RESULTS: The mean age of presentation was 51.05 years (range 7 months-77 years). The number of male patients was 168 while females were 132. The duration of symptoms ranged from 20 days to 3 years. The number of patients with little/no education presented mainly in advanced stages as compared to their educated counterpart and this difference was statistically significant (p<0.001). The number of patients presenting directly to the department was 108, those diagnosed outside and referred to us was 84 while those diagnosed and received some form of oncologic treatment outside and referred thereafter was 108. The difference in the primary delay between patients presenting directly to the MC versus those diagnosed outside was significant (p=0.0126). The mean duration of starting definitive treatment after presentation to the outpatient was 4.68 days (range 0-22 days) and was very significantly (p< 0.001) less than the secondary delays caused to the other two subsets of patients. CONCLUSION: Factors causing delayed presentation are both patient and system related. It is imperative to educate the common people regarding the early signs and symptoms of cancer. At the same time, the system needs to overhaul its efficiency to avoid secondary delays that adversely affect the treatment outcome. An upgradation of the existing oncology facilities in the public sector can achieve this target efficiently.

Cytokine responses to novel antigens in an Indian population living in an area endemic for visceral leishmaniasis.

BACKGROUND: There are no effective vaccines for visceral leishmaniasis (VL), a neglected parasitic disease second only to malaria in global mortality. We previously identified 14 protective candidates in a screen of 100 Leishmania antigens as DNA vaccines in mice. Here we employ whole blood assays to evaluate human cytokine responses to 11 of these antigens, in comparison to known defined and crude antigen preparations. METHODS: Whole blood assays were employed to measure IFN-γ, TNF-α and IL-10 responses to peptide pools of the novel antigens R71, Q51, L37, N52, L302.06, J89, M18, J41, M22, M63, M57, as well as to recombinant proteins of tryparedoxin peroxidase (TRYP), Leishmania homolog of the receptor for activated C kinase (LACK) and to crude soluble Leishmania antigen (SLA), in Indian patients with active (n = 8) or cured (n = 16) VL, and in modified Quantiferon positive (EHC(+ve), n = 20) or modified Quantiferon negative (EHC(-ve), n = 9) endemic healthy controls (EHC). RESULTS: Active VL, cured VL and EHC(+ve) groups showed elevated SLA-specific IFN-γ, but only active VL patients produced IL-10 and EHC(+ve) did not make TNF-α. IFN-γ to IL-10 and TNF-α to IL-10 ratios in response to TRYP and LACK antigens were higher in cured VL and EHC(+ve) exposed individuals compared to active VL. Five of the eleven novel candidates (R71, L37, N52, J41, and M22) elicited IFN-γ and TNF-α, but not IL-10, responses in cured VL (55-87.5% responders) and EHC(+ve) (40-65% responders) subjects. CONCLUSIONS: Our results are consistent with an important balance between pro-inflammatory IFNγ and TNFγ cytokine responses and anti-inflammatory IL-10 in determining outcome of VL in India, as highlighted by response to both crude and defined protein antigens. Importantly, cured VL patients and endemic Quantiferon positive individuals recognise 5 novel vaccine candidate antigens, confirming our recent data for L. chagasi in Brazil, and their potential as cross-species vaccine candidates.

Reassessment of immune correlates in human visceral leishmaniasis as defined by cytokine release in whole blood.

Depressed cell-mediated immunity in human visceral leishmaniasis (VL) (also known as kala-azar), revealed as the inability of peripheral blood mononuclear cells (PBMCs) to respond to Leishmania antigen, remains a hallmark of and is thought to underlie the progressive nature of this disease. We recently reported the ability of a whole-blood, gamma interferon (IFN-γ) release assay to detect subclinical infections among healthy individuals living in an area where kala-azar is endemic (Bihar, India) and the surprising result that patients with active VL also secreted significant levels of antigen-specific IFN-γ in this assay. We were interested in ascertaining whether these findings would be true for a larger cohort of subjects and in employing the whole-blood assay to detect additional cytokines that might better correlate with the disease status of infected individuals. We evaluated IFN-γ, tumor necrosis factor alpha (TNF-α), and interleukin-10 (IL-10) release in 35 patients with active VL, 54 patients with VL who were cured, 27 patients with other diseases, 52 healthy controls who lived in regions where VL or kala-azar is not endemic (NEHCs [for nonendemic healthy controls]), and 147 healthy controls who lived in regions where kala-azar is endemic (EHCs [for endemic healthy controls]). The cellular responses of the EHCs were correlated with their serological antibody titers against Leishmania donovani and Phlebotomus argentipes saliva. The whole-blood cells from the majority of both active (80%) and cured (85%) VL patients, as well as 24% of EHCs with presumed subclinical infections, produced significantly elevated levels of IFN-γ. The findings do not support a severe Th1 response defect in kala-azar. Importantly, only the patients with active VL also produced IL-10, which in conjunction with IFN-γ better reflects the immune responses that distinguish individuals with active disease from cured or subclinically infected, immune individuals.

Effects of lithium therapy on Na+-K+-ATPase activity and lipid peroxidation in bipolar disorder.

OBJECTIVES: Oxidative stress induced lipid peroxidation along with a reduced Na(+)-K(+)-ATPase activity has been implicated in the pathophysiology of bipolar disorders (BPD). Although, lithium therapy results in significant improvement in the symptoms of the disease, studies regarding its effect on the altered sodium pump activity and lipid peroxidation status have come out with conflicting results. The present study was undertaken to evaluate the status of lipid peroxidation and analyze the role of lithium and Na(+)-K(+)-ATPase activity in its regulation in BPD patients in our region. METHOD: We measured RBC membrane Na(+)-K(+)-ATPase activity and serum thiobarbituric acid reacting substances (TBARS) level in 73 BPD patients and serum lithium, in addition, in 48 patients receiving lithium therapy among them. RESULTS: Na(+)-K(+)-ATPase activity and serum TBARS level were significantly decreased and increased respectively in all BPD patients compared to age and sex matched healthy controls. Same trend was observed in the BPD patients stabilized on lithium therapy compared to the lithium naive ones. Although, the enzyme activity showed a reciprocal relationship with TBARS in all patients of BPD, a significant positive correlation and dependence of the enzyme activity was evident with serum lithium level only in the lithium stabilized BPD group. CONCLUSIONS: BPD patients showed significantly compromised Na(+)-K(+)-ATPase activity and increased lipid peroxidation. Lithium induced improvement in the enzyme activity was associated with significant reduction in lipid peroxidation. Enhancement of the Na(+)-K(+)-ATPase activity by optimum dosage of lithium may be a potential contributing factor for reducing oxidative stress in BPD patients.

IL-27 and IL-21 are associated with T cell IL-10 responses in human visceral leishmaniasis.

IL-10 is believed to underlie many of the immunologic defects in human visceral leishmaniasis (VL). We have identified CD4(+)CD25(-)Foxp3(-) T cells as the major source of IL-10 in the VL spleen. IL-27, a member of the IL-6/IL-12 cytokine family, has been shown to promote development of IL-10-producing T cells, in part by upregulating their production of autocrine IL-21. We investigated whether IL-27 and IL-21 are associated with human VL. IL-27 was elevated in VL plasma, and at pretreatment, spleen cells showed significantly elevated mRNA levels of both IL-27 subunits, IL-27p28 and EBI-3, as well as IL-21, compared with posttreatment biopsies. CD14(+) spleen cells were the main source of IL-27 mRNA, whereas CD3(+) T cells were the main source of IL-21. IL-27 mRNA could be strongly upregulated in normal donor macrophages with IFN-γ and IL-1ß, conditions consistent with those in the VL spleen. Last, a whole-blood assay revealed that most VL patients could produce Ag-specific IFN-γ and IL-10 and that the IL-10 could be augmented with recombinant human IL-21. Thus, proinflammatory cytokines acting on macrophages in the VL spleen have the potential to upregulate IL-27, which in turn can induce IL-21 to expand IL-10-producing T cells as a mechanism of feedback control.

Role of antiparasitic therapy for seizures and resolution of lesions in neurocysticercosis patients: an 8 year randomised study.

Neurocysticercosis is a common cause of acquired seizure disorder in developing countries, including India. The role of antiparasitic (albendazole) therapy for seizure control and resolution of lesions is still controversial due to a lack of adequately controlled studies. The objective of the present study was to evaluate the role of albendazole therapy for neurocysticercosis patients with two or more lesions to achieve seizure-free status and resolution of lesions. This was a randomised controlled study in which patients suffering from neurocysticercosis were prospectively followed up for more than 5 years (from January 1997 to January 2005). Patients were divided into two groups: patients in group A (n=150) were treated with a combination of tapered doses of dexamethasone and albendazole, plus antiepileptic drugs; patients in group B (n=150) were treated with antiepileptic drugs plus a placebo control. Patients were followed up every month for the first 6 months and then at 3-month intervals thereafter up to 5 years. Variables of interest were (i) recurrence of seizures; (ii) encephalopathy (headache/vomiting/altered sensorium); (iii) need for subsequent hospital admission; (iv) death; (v) resolution of lesions on follow-up CT. During the first 6 months and at intervals thereafter, increased seizure frequency and hospital readmissions, and increased incidence of encephalopathy were observed in group A (p=0.01), and two patients in this group died with intractable seizures and encephalopathy. A greater proportion of lesions completely resolved in group B (p=0.05), whereas a greater proportion of lesions calcified in group A (p=0.05). Albendazole plus antiepileptic drugs did not have greater beneficial effects than antiepileptic drugs alone, but may have an adverse effect with respect to seizure control, encephalopathy, recurrent hospital admissions, calcification of lesions and cost of treatment.