Radiolabeled somatostatin analogs have become powerful tools in the diagnosis and staging of neuroendocrine tumors, which express somatostatin receptors. The aim of this study was to evaluate a new somatostatin analog, 6-hydrazinopyridine-3-carboxylic acid-Ser3-octreotate (HYNIC-SATE) radiolabeled with 99mTc, using ethylenediamine-N,N'-diacetic acid and tricine as coligands, to be used as a radiopharmaceutical for the in vivo imaging of somatostatin receptor subtype 2 (SSTR2)-positive tumor. Synthesis of the peptide was carried out on a solid phase using a standard Fmoc strategy. Peptide conjugate affinities for SSTR2 were determined by receptor binding affinity on rat brain cortex and C6 cell membranes. Internalization rate of 99mTc-HYNIC-SATE was studied in SSTR2-expressing C6 cells that were used for intracranial tumor studies in rat brain. A reproducible in vivo C6 glioma model was developed in Sprague-Dawley rat and confirmed by histopathology and immunohistochemical analysis. Biodistribution and imaging properties of this new radiopeptide were also studied in C6 tumor-bearing rats. Radiolabeling was performed at high specific activities, with a radiochemical purity of >96%. Peptide conjugate showed high affinity binding for SSTR2 (HYNIC-SATE IC50=1.60±0.05 n m) and specific internalization into rat C6 cells. After administration of 99mTc-HYNIC-SATE in C6 glioma-bearing rats, a receptor specific uptake of radioactivity was observed in SSTR-positive organs and in the implanted intracranial tumor and rapid excretion from nontarget tissues via kidneys. 99mTc-HYNIC-SATE is a new receptor-specific radiopeptide for targeting SSTR2-positive brain tumor and might be of great promise in the scintigraphy of SSTR2-positive tumors.
A practical copper-catalyzed, 2-picolinamidedirected ortho C−H amination of anilines with benzoylprotected hydroxylamines has been disclosed that proceeds smoothly without any external stoichiometric oxidant or additives. Remarkably, besides anilines, bicyclic naphthyl or heterocyclic amines furnished amination products with fiveand six-membered cyclic and acyclic amines at the ortho position selectively. This electrophilic C−H amination also proceeds smoothly in water under slightly modified reaction conditions.E fficient construction of C−N bonds represents one of the mainstays of research in organic synthesis over the last decades, because of the exponential use of nitrogen-containing molecules in pharmaceutical, medicinal, and materials science. 1 Following the pioneer works of Buchwald and Hartwig regarding palladium-catalyzed C−N bond formation from aryl halides and amines, 2 an impressive array of Earthabundant, inexpensive copper-catalyzed C−N coupling reactions have been explored. 3 A mechanistically distinct coppercatalyzed/mediated oxidative C−N coupling using organometallic reagents has also been developed under mild conditions. 4 A paradigm shift from transition-metal-catalyzed cross-coupling with organometallic reagents to direct C−H amination strategy has been observed in the last decades. In this vein, the research groups of Yu and Chatani independently reported copper-mediated C−H amination of 2-arylpyridines. 5 Remarkably, the Daugulis group expanded the scope of C−H amination using removable, bidentate directing groups. 6 Recently, the Chang group also reported copper-mediated C−H amination with aqueous ammonia. 7 2-Aminoanilide moiety is ubiquitously found in drug candidates for the treatment of cancer, Alzheimer's disease, wet age-related macular degeneration (wet AMD), and infectious diseases. 8 In 2014, the research groups of Rodri ́guez and Chen independently reported copper-catalyzed, 2picolinamide-directed ortho C−H amination of aniline. 9 However, stoichiometric amount of expensive PhI(OAc) 2 was used as an oxidant, which generates PhI as a byproduct. More recently, an electrochemical synthesis of C−H amination of the same substrate was reported by the Mei group, using tetrabutylammonium iodide (TBAI) as a redox mediator. 10 However, all these protocols are limited to the six-membered cyclic amines only. Acyclic amines, pyrrolidine (<5% yield),
Peptides are attracting increasing interest in nuclear oncology for targeted tumor diagnosis and therapy. We therefore synthesized new cyclic octapeptides conjugated with HYNIC by Fmoc solid-phase peptide synthesis. These were purified and analyzed by RP-HPLC, MALDI mass, (1)H NMR, (13)C NMR, HSQC, HMBC, COSY and IR spectroscopy. Conformational analysis of the peptides was performed by circular dichroism spectroscopy, in pure water and trifluoroethanol-water (1:1), revealed the presence of strong secondary structural features like β-sheet and random coils. Labeling was performed with (99m)Tc using Tricine and EDDA as coligands by SnCl(2) method to get products with excellent radiochemical purity >99.5 %. Metabolic stability analysis did not show any evidence of breaking of the labeled compounds and formation of free (99m)Tc. Internalization studies were done and IC(50) values were determined in somatostatin receptor-expressing C6 glioma cell line and rat brain cortex membrane, and the results compared with HYNIC-TOC as standard. The IC(50) values of (99m)Tc-HYNIC-His(3)-Octreotate (21 ± 0.93 nM) and (99m)Tc-HYNIC-TOC (2.87 ± 0.41 nM) proved to be comparable. Biodistribution and image study on normal rat under gamma camera showed very high uptake in kidney and urine, indicating kidney as primary organ for metabolism and route of excretion. Biodistribution and image study on rats bearing C6 glioma tumor found high uptake in tumor (1.27 ± 0.15) and pancreas (1.71 ± 0.03). Using these findings, new derivatives can be prepared to develop (99m)Tc radiopharmaceuticals for imaging somatostatin receptor-positive tumors.
BackgroundSevere cholestatic jaundice may complicate with bile cast nephropathy (BCN) causing severe acute kidney injury (AKI). In this study, we investigate BCN in severe falciparum malaria complicated with jaundice and AKI.MethodsThis prospective study was conducted in a tertiary health care institution with high prevalence of malaria. A cohort of 110 patients with falciparum malaria complicated with cerebral malaria, jaundice and AKI were enrolled. Species diagnosis was made from peripheral blood smear or rapid diagnostic test. Severe malaria was diagnosed from WHO criteria. BCN was diagnosed with the detection of bile casts in urine or in biopsy. The recovery pattern and outcome with and without BCN was assessed.ResultsOut of 110 patients, 20 (18.2%) patients had BCN and 15 (13.6%) patients had hepato-renal syndrome. Patients with BCN had high conjugated bilirubin (26.5 ± 4.1 mg/dL), urea (75.9 ± 10.3 mg/dL) and creatinine (7.2 ± 0.8 mg/dL), longer duration of illness (6.4 ± 1.1 days), higher mortality (25.0%) and prolonged recovery time of hepatic (9.6 ± 2.4 days) and renal dysfunction (15.1 ± 6.5 days) compared with patients without BCN.ConclusionsProlonged duration of illness and increased bilirubin cause BCN among patients with severe falciparum malaria with jaundice and AKI, which is associated with high mortality and morbidity.
Vaginal hysterectomy is the gold standard in the era of minimal access surgery. Some of the contraindications to VH can be overcome by assistance of laparoscope and a potential abdominal hysterectomy can be converted to a vaginal procedure.
METHODS: All the USG proven cases of PCOS were subjected to investigations like FSH, LH, FBS, PPBS, Serum Insulin, TSH, Free T3, Free T4. After an overnight fasting, basal venous blood sample was taken. TFT including TSH, Free T3 and Free T4 was estimated using chemiluminescence method. According to this, TSH normal range was taken as 0.34-4.25 µIU/ml, Free T3 normal range was 2.4-4.2 pg/ml, Free T4 normal range was 0.8-1.7 ng/dl 137. TSH above 4.25 µIU/ml, Free T3 below 2.4 pg/ml and Free T4below 0.8 ng/dl was considered as overt hypothyroidism and high TSH with normal Free T3 and Free T4 are considered as subclinical hypothyroidism. RESULTS: The mean age of presentation was 27.28± 10.56 years. 78.57% of cases had menstrual complaints. 20.40 % 0f cases had Secondary Amenorrhoea, 56.12 % had Oligomenorrhoea, 2.04 % had Polymenorrhoea and 21.42% had normal menstrual cycles. 76.53 % of cases had Hyperandrogenism. 66.32 % had hirsuitism, out of which 69.23 % had mild hirsuitism, 29.23 % had moderate hirsuitism and 1.53 % had severe hirsuitism. 31.63% of cases had Acne.70 % of married cases had Infertility. Out of that 79.59 % had primary infertility and 20.40 % had secondary infertility. 38.77 % had infertility of duration 1-2 years, 51.02 % had infertility of 3-5 years and 10.20 % had infertility of >5 years. 64.28 % of cases had increased BMI (≥25 kg/m 2). The prevalence of hypothyroidism in PCOS was 13.26 %. Out of that 57.69 % had subclinical hypothyroidism and 42.30 % had overt hypothyroidism. 96.15 % of PCOS with hypothyroidism had menstrual irregularities like oligomenorrhoea and secondary Amenorrhoea. This association was found to be statistically significant. 96.15 % of PCOS with hypothyroidism had features of hyperandrogenism like acne and hirsuitism. This association was found to be statistically significant.84.61 % of PCOS with hypothyroidism had increased BMI (≥25 kg/m 2 .) This association was found to be statistically significant. PCOS and Hypothyroidism are closely related. CONCLUSION: There is increased prevalence of hypothyroidism in PCOS. The relationship between thyroid profile and PCOS is being tried to be explored more and thus the problems of PCOS can be solved to some more extent.
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