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OBJECTIVE: To determine the auxological response to recombinant human growth hormone (rhGH) therapy in children with growth hormone deficiency (GHD) presenting at the National Institute of Child Health, Karachi, Pakistan. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Paediatric Endocrinology, National Institute of Child Health, Karachi, Pakistan, from January 2022 to December 2023. METHODOLOGY: All pre-pubertal children with short stature aged 3-12 years diagnosed with GHD and who were prescribed rhGH therapy were included in the study. Children with any other underlying reason for short stature or any other comorbidity were excluded. Patients' demographics and baseline growth parameters were recorded in a pre-designed proforma. Patients were then followed up every three months till one year. Response to rhGH therapy was evaluated through comparison of growth parameters before and after one year of therapy. RESULTS: A total of 90 children including 47 (52.2%) males and 43 (47.8%) females with GHD were enrolled. Mean age of these patients was 7.92 ± 2.647 years. A statistically significant change in height (SD), Weight (SD), and BMI (SD) was observed before and after one year of therapy (p <0.001). Response to therapy in terms of height did not differ significantly with respect to gender (p = 0.955) or stimulated growth hormone levels (p = 0.911). However, response to rhGH therapy was significantly better in terms of increase in height, weight, and BMI in patients presenting earlier i.e. at age ≤8 years. CONCLUSION: Recombinant human growth hormone therapy was effective in children with short stature to achieve desirable growth. Children diagnosed and treated at a younger age (≤8years) achieve better height outcomes as compared to those presenting late. KEY WORDS: Short stature, Growth hormone deficiency, Recombinant human growth hormone.
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Estatura , Trastornos del Crecimiento , Hormona de Crecimiento Humana , Proteínas Recombinantes , Humanos , Femenino , Masculino , Niño , Hormona de Crecimiento Humana/uso terapéutico , Hormona de Crecimiento Humana/deficiencia , Preescolar , Estatura/efectos de los fármacos , Proteínas Recombinantes/uso terapéutico , Trastornos del Crecimiento/tratamiento farmacológico , Pakistán , Resultado del Tratamiento , Enanismo Hipofisario/tratamiento farmacológicoRESUMEN
Background and Objective: The autoimmune mechanism in T1DM causes gradual loss of pancreatic ß-cell, which progresses to hyperglycemia and ultimate reliance on consistent insulin therapy. T1DM has been the commonest type of diabetes in children and this study will help in refining indulgent towards the problem and its pathophysiology in our people. The objective was to find out the prevalence of C-peptide and antibody levels (anti GAD, ICA, IAA and IA2) in children and adolescents of Pakistan with T1DM. Methods: We conducted this cross-sectional study at Department of Pediatric Endocrinology, National Institute of Child Health, Karachi between August 2019 to February 2020 and included 98 children who had T1DM for more than one month. Subjects whose GFR was <30ml/min were omitted from the study. Among those registered subjects, C-peptide, human islet cell antibody (ICA), insulin auto antibodies (IAA) and anti-glutamic acid decarboxylase were assessed. Demographical and laboratorial facts were noted on a pre-constructed proforma. Results: There were 77(78.3%) cases who had level of C-peptide <0.8 and anti-GAD was found in 47(48%) subjects. 35(35.7%) cases found positive for IA2 .and 7(7.1%) patients had insulin auto antibodies positive while ICA was negative in total 98(100%) subjects. Conclusion: Children with T1 DM possessed increased levels of anti-GAD antibodies, insulin autoantibodies and anti (IA2) but islet cells antibodies were negligible in our population when checked at a point of time. C-peptide may be normal in some, but its level declines with long duration of diabetes in children.
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Interleukin-2 has emerged as a potent protein-based drug to treat various cancers, AIDS, and autoimmune diseases. Despite its immense requirement, the production procedures are inefficient to meet the demand. Therefore, efficient production procedures must be adopted to improve protein yield and decrease procedural loss. This study analyzed cytoplasmic and periplasmic IL-2 expression for increased protein yield and significant biological activity. The study is focused on cloning IL-2 into a pET-SUMO and pET-28a vector that expresses IL-2 in soluble form and inclusion bodies, respectively. Both constructs were expressed into different E. coli expression strains, but the periplasmic and cytoplasmic expression of IL-2 was highest in overnight culture in Rosetta 2 (DE3). Therefore, E. coli Rosetta 2 (DE3) was selected for large-scale production and purification. Purified IL-2 was characterized by SDS-PAGE and western blotting, while its biological activity was determined using MTT bioassay. The results depict that the periplasmic and cytoplasmic IL-2 achieved adequate purification, yielding 0.86 and 0.51 mg/mL, respectively, with significant cytotoxic activity of periplasmic and cytoplasmic IL-2. Periplasmic IL-2 has shown better yield and significant biological activity in vitro which describes its attainment of native protein structure and function.
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Pyrazinamide, an antituberculosis but documented toxic drug, is subjected to computational investigation along with the metal complexes via a DFT approach to predict the structure-activity and structure-toxicity relationship. 6-31G(d,p) basis set was used for Zn, Ni, Mn, Fe, and Co, while the SDD basis set was applied to Cu, Cr, Cd, and Hg. Several reactivity parameters and charge distribution were calculated and the reactivity profile was estimated. The complexes were found to be soft and polarizable which could be responsible for their binding with bacterial targets to inhibit their growth. In contrast, pyrazinamide which is found to be hard among all is susceptible to being toxic. Moreover, the electronegative nature of the complexes can endow them with a better antibacterial effect. Since metal complexes have been found to be less toxic and more biologically interactive by computational methods, they can be employed as potent drugs for the cure of tuberculosis.
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Complejos de Coordinación , Mercurio , Pirazinamida/farmacología , Complejos de Coordinación/farmacología , AntibacterianosRESUMEN
BACKGROUND: Type-1 diabetes mellitus (T1DM) and autoimmune thyroid disease can occur concomitantly and patients with TIDM have a high risk of other autoimmune conditions like thyroid disease and celiac disease. This study aimed to analyze the association of anti-GAD positive T1DM with anti-thyroid antibodies and celiac disease. METHODS: This cross-sectional study was conducted at the Department of Paediatric Endocrinology & Diabetes, National Institute of Child Health, Karachi Pakistan from July 2022 to December 2022. A total of 115 children of both genders aged between 1-18 years having known T1DM were analyzed. Children with chronic kidney disease or chronic liver disease were excluded. Those children were also not included whose parents/caregivers did not wish their children to be part of this research. The blood sample of each child was taken in a sterilized container and sent to an institutional laboratory for biochemical investigations. RESULTS: In a total of 115 patients, 67 (58.3%) were female and 48 (41.7%) males. The mean age was 8.87±3.43 (ranging between 1.5-17 years). The mean HbA1c was 11.86±7.31%. It was found that anti-GAD IgG was having signification association with celiac disease (p<0.001). Significant correlation of anti-GAD positive antibodies with Ttg-IgG antibodies (correlation coefficient=0.303, p=0.001), thyroid peroxidase antibodies (correlation coefficient=0.228, p=0.001). CONCLUSIONS: High proportions of children with anti-GAD positive T1DM patients were found to have thyroid disorders and celiac disease. A significant correlation was found between anti-GAD positive antibodies, celiac disease and anti-thyroglobulin antibodies.
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Enfermedad Celíaca , Diabetes Mellitus Tipo 1 , Enfermedades de la Tiroides , Niño , Humanos , Femenino , Masculino , Lactante , Preescolar , Adolescente , Diabetes Mellitus Tipo 1/complicaciones , Enfermedad Celíaca/complicaciones , Estudios Transversales , Autoanticuerpos , Enfermedades de la Tiroides/complicaciones , Inmunoglobulina GRESUMEN
Progressive pseudorheumatoid dysplasia or spondyloepiphyseal dysplasia tarda is caused by a mutation in Wnt1 inducible signalling pathway protein 3 (WISP3) and passes in an autosomal recessive manner. Prevalence underestimated as one per million and most of the cases remain undiagnosed or treated as Juvenile Idiopathic Arthritis (JIA). Differentiation between JIA and PPRD is really challenging however, this case is genetically confirmed from our country. 7-year-old, short stature boy, with multiple joint swellings of hands and feet, initially suspected to have JIA and had been worked up and took treatment for that for the past 2 years. He had progressive stiffness of small joints. Baseline biochemistry, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor and ANA, were within normal limits. He was moderately growth hormone deficient. Thyroid function tests and insulin-like growth factor 1 (IGF-1) were within reference ranges. Skeletal survey showed typical findings of pseudorheumatoid skeletal dysplasia. Physical therapy and genetic counselling were done.
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Artritis Juvenil , Artropatías , Osteocondrodisplasias , Masculino , Humanos , Niño , Artritis Juvenil/diagnóstico , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/genética , Artropatías/diagnóstico , Artropatías/genética , MutaciónRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of zoledronic acid in children with osteogenesis imperfecta (OI). STUDY DESIGN: Descriptive Study. PLACE AND DURATION OF STUDY: National Institute of Child Health, Department of Endocrine and Diabetes, Karachi, Pakistan, from January 2011 to December 2020. METHODOLOGY: Children, with OI registered for the treatment, were included. Zoledronic acid was given to them by intravenous infusion over 30 minutes with a dose of 0.05 mg/Kg/day for a median duration of 60 (24-96) months. To ensure safety, patients were kept for 24 hours after dose administration to monitor any short-term side effects. The patients were assessed after every 3-6 months for frequency of fracture, bone pain, and BMD. RESULT: Out of 82 children [40 females (48.8%) and 42 males (51.2%)], 11 patients (13.4%) had fever and 2 patients (2.4%) had flu-like illness. No other side effects were observed. The annual fracture rate decreased overall from 2.8±1.5 to 0.2±0.5 (Ë0.001) in both males (2.6±1.3 to 0.1±0.4) and females (3.1±1.7 to 0.2±0.6). Z-score on DEXA scan showed improvement in BMD overall (-3.9±2.0 to 2.2 ±1.7), in males (-3.7±1.9 to -2.1±1.7) and in females (4.1±2.1 to -2.3±1.8). There were no other long-term side effects like ocular problems, osteonecrosis of the jaw, and delayed healing of the fractures. CONCLUSION: Zoledronate use in children is associated with minimal short-term and long-term side effects with a significant improvement in BMD and decline in fracture rate. KEY WORDS: Osteogenesis imperfecta (OI), Bisphosphonates (BPs), DEXA scan, Bone mineral density (BMD).
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Conservadores de la Densidad Ósea , Fracturas Óseas , Osteogénesis Imperfecta , Conservadores de la Densidad Ósea/efectos adversos , Niño , Difosfonatos/efectos adversos , Femenino , Humanos , Masculino , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/tratamiento farmacológico , Resultado del Tratamiento , Ácido Zoledrónico/uso terapéuticoRESUMEN
BACKGROUND: The IL-12/IFN-γ axis plays a vital role in the control of intramacrophagic pathogens including Leishmania infections. OBJECTIVE: The aim of this study was to investigate genetic defects in the IL-12/IFN-γ axis in cutaneous leishmaniasis patients, using immunological and genetic evaluation. METHODS: Enzyme-linked immunosorbent assay was used to quantify IFN-γ , while flow cytometry was performed to analyze surface IL-12Rß1/IL-12Rß2 expression and phosphorylation of signal transducers as well as the activator of transcription 4 (pSTAT4). Sequencing was carried out for genetic analysis. RESULTS: The peripheral blood mononuclear cells from the two patients (P1 and P2) demonstrated impaired production of IFN-γ. Furthermore, abolishment of the surface expression of Il-12Rß1 was observed in lymphocytes, with consequent impairment of STAT4 phosphorylation in the lymphocytes of P1 and P2. IL-12Rß1 deficiency was identified, which was caused by a novel homozygous missense mutation (c.485>T/p.P162L) and a novel homozygous nonsense mutation (c.805G>T/P.E269*) in the IL-12Rß2 gene of P1 and P2, respectively. In silico analyses predicted these novel mutations as being pathogenic, causing truncated proteins, with consequent inactivation. CONCLUSION: Our data have expanded the phenotype and mutation spectra associated with IL-12Rß1 deficiency, and suggest that patients with CL should be screened for mutations in genes of the IL-12/IFN-γ axis.
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Leishmaniasis Cutánea , Leucocitos Mononucleares , Receptores de Interleucina-12 , Humanos , Interferón gamma/genética , Interleucina-12 , Leishmaniasis Cutánea/genética , Receptores de Interleucina-12/genética , RecurrenciaRESUMEN
Van Wyk Grumbach syndrome is well known for protracted hypothyroidism, characterised by multicystic ovaries (normal size ovaries contain many follicles of various sizes), isosexual precocious puberty and delayed skeletal growth. A series of ten children with Van Wyk Grumbach syndrome is been presented with their clinical features, biochemical and radiological profile and management. Patients showed a noteworthy improvement upon thyroxine therapy. It is vital to keep this entity in consideration and; hence, should investigate for thyroid status during the evaluation of ovarian cysts. Thyroxin replacement after establishing the diagnosis early can prevent the patient from going through extensive workup and surgeries. Key Words: Hypothyrodism, Multicystic ovaries, Isosexual precocious puberty.
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Hipotiroidismo , Quistes Ováricos , Síndrome del Ovario Poliquístico , Pubertad Precoz , Niño , Femenino , Humanos , Hipotiroidismo/diagnóstico , Hipotiroidismo/tratamiento farmacológico , Quistes Ováricos/diagnóstico por imagen , Pubertad Precoz/diagnóstico , Pubertad Precoz/tratamiento farmacológico , Tiroxina/uso terapéuticoRESUMEN
OBJECTIVE: To analyse chromosomal abnormalities of the patients who were referred for the screening of short stature and delayed puberty and to verify the association between karyotype and phenotype in confirmed Turner Syndrome (TS) patients. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Pediatric Endocrinology and Diabetes Unit-II, National Institute of Child Health, Karachi, from January 2011 to June 2016. METHODOLOGY: Patients referred for the evaluation of short stature or delayed puberty were for the assessment of karyotype and phenotype correlations; standard karyotyping was executed and analysed on the basis of routine G-banding technique. Echocardiography and pelvic ultrasonography was also performed. RESULTS: The study population consisted of 79 registered patients, with short stature and delayed puberty 48/79 (60.75%), short stature 68/79 (86.07%), and ambiguous genitalia 5/79 (6.32%). Conferring to the karyotype analysis, classical Turner Syndrome 45, X was found in 42/79 (53.16%), isochromosomes 13/79 (16.45%), and mosaicism was present in 11/79 (14.1%). Only 7/79 (8.86%) cases were diagnosed in infancy. CONCLUSION: The results of the study showed the consistency of short stature and delayed puberty in most of patients. Monosomy of X chromosome was the commonest followed by isochromosomes, mosaicism and structural abnormalities of X chromosome. No remarkable difference was found among classical and non-classical TS patients' height.