Molecular profiling of an Indian EB cohort - a single centre experience.

INTRODUCTION: Epidermolysis bullosa (EB) encompasses rare hereditary skin conditions marked by skin fragility, nail dystrophy, and minor trauma-induced skin blisters. This study aims to identify genetic variants in Indian EB patients and examine the relationship between genotypic and phenotypic manifestations. MATERIAL AND METHOD: EB patients seen consecutively over a period of 5 years at Outpatient Department of Dermatology. Baseline demographic data, birth history, family history, skin manifestation at birth, past medical history, current cutaneous manifestations, and the evolution of the disease were assessed and recorded. Genetic variants were identified using targeted gene panel sequencing of 23 EB-related genes, and a genetic-phenotype analysis was performed. RESULTS: Our study included 65 patients with EB. Among 65 EB patients, 38 dystrophic EB cases (58.46%), 12 junctional EB (18.46%), 12 epidermolysis bullosa simplex (18.46%), and 3 Kindler EB (4.62%) were reported. Dominant and recessive forms of dystrophic EB accounted for 16.92% and 41.4%, respectively. We identified 75 unique genetic variants, 58.67% newly discovered and 41.33% previously reported. Compound heterozygous variations were more frequent (55.55%) than homozygous ones (44.44%) in recessive dystrophic EB patients. Junctional EB patients harboured LAMB3 gene mutations more frequently, while epidermolysis bullosa simplex patients showed KRT5 and KRT14 gene missense heterozygous mutations. Kindler EB patients had homozygous mutations in the FERTM1 gene. CONCLUSION: Our study unveiled several novel genetic variants; severe phenotypes associated with nonsense genetic variants. These findings offer valuable insights for future clinical assessments and tailored management strategies.

Two-dimensional Shear Wave Elastography: Utility in Differentiating Gallbladder Cancer From Chronic Cholecystitis.

OBJECTIVE: To study the utility of 2D shear wave elastography (SWE) and ascertain cut-off values of shear wave elasticity (SWe) to differentiate benign and malignant thickening of the gallbladder wall. METHODS: This study was a prospective study of patients with symptomatic gallstone disease (GSD, n = 51) and gallbladder cancer (GBC, n = 46) and controls without any biliary disease (n = 46). All the participants underwent 2D USG and SWE of the gallbladder. Grey-scale ultrasound and SWE were done in the different regions in the gallbladder. RESULTS: The median age of the patients with GSD was 49 years (interquartile range [IQR]: 33-55), GBC was 55 years (IQR: 46-65), and controls was 37 years (IQR: 27-48.25). In patients with GBC, asymmetrical mural thickening was the predominant imaging pattern (n = 24, 52.2%). The mean SWe of the abnormal area in GBC (34.99 ± 17.77 kPa [n = 46]) was significantly higher than that of the uninvolved region (18.27 ± 8.12 kPa [n = 35]; P < .01). The mean SWe of the uninvolved region in GBC (18.27 ± 8.12 kPa [n = 35]) was also significantly higher (P < .01) than that of GSD (12.27 ± 4.13 kPa [n = 51]) and controls (10.52 ± 3.75 kPa [n = 46]). On ROC analysis, AUC of 0.927, at a cut-off of 20 kPa, sensitivity was 91.3%, specificity was 83.5%, positive likelihood ratio was 5.54, and negative likelihood ratio was 0.10 to diagnose GBC. CONCLUSION: The 2D SWE is a reliable adjunctive tool to grey-scale USG in differentiating the malignant from benign gallbladder wall and may help to pick up early malignancy in GSD.

Mycobacterium tuberculosis does not show evidence of molecular DNA in human cadaveric ocular tissues in an endemic setting.

BACKGROUND: Mycobacterium tuberculosis (MTB) in latent infection has been demonstrated in pulmonary/extra-pulmonary locations (lung, spleen, liver, kidney, adipose tissue) in autopsy studies, but its presence in ocular tissues in the latent state is not known. METHODS: We conducted molecular and histopathological study of 100 cadaver eyes (50 humans) who died from causes other than tuberculosis (TB) (and were potential candidates for corneal transplantation) to detect MTB in ocular tissues in an endemic setting. After removal of the corneal button, an 8 to 10 mm block of tissue (choroid, retina and part of the vitreous) was excised from the remaining globe for DNA isolation. Gel-based IS6110 and devR3 polymerase chain reaction (PCR) assays were done, followed by real-time PCR using beta actin gene as an internal control. Sixteen randomly selected DNA samples were double checked using a commercial kit for MTB and non-tuberculous mycobacteria (NTM) DNA. The remaining larger part of the globe was subjected to histopathology. RESULTS: The mean age was 65.14 ± 18 years. All 100 samples were negative for both IS6110 and devR, and all 16 samples were negative with NTM MTB commercial kit. All samples were negative with Ziehl-Neelsen stain for acid fast bacilli and none showed any inflammation or granulomatous pathology. CONCLUSIONS: MTB could not be detected in human ocular tissues in latent state in India, a TB-endemic country. This may suggest the inability of MTB to seed ocular tissues in the latent state, unlike other organs which serve as reservoirs for the bacilli in the absence of manifest disease.

Neuroprotective Role of Lazaroids Against Aluminium Chloride Poisoning.

Aluminium (Al) is neurotoxic primarily because of its interference with biological enzymes in key mechanisms of metabolic pathways. Mitochondria being a major site of reactive oxygen species (ROS) production, it seems that the oxidative damage to mitochondrial proteins may underlie the pathogenesis of Al induced neurodegeneration. The present study investigates the effectiveness of the anti-oxidant property of lazaroids (U-74500A), a known lipid peroxidation inhibitor as neuroprotective agent against Al induced neurotoxicity. Al chloride was administered orally at a dose level of 100 mg/kg body wt/day in water and U-74500A was administered at a dose of 0.25 mg/kg body wt i.p. in citrate buffer for a period of 8 weeks on alternate days. Following Al exposure there was a significant increase in lipid peroxidation (LPO), ROS levels and reduction in the activity of mitochondrial complexes in all the three regions of rat brain, i.e., cerebral cortex, mid brain, and cerebellum. This decrease in the activities of electron transport complexes in turn affected the ATP synthesis and ATP levels adversely in the mitochondria. These alterations were also depicted in the histology which shows signs of hypoxia, paucity of neurons in cortical region and loosening of fibers in the white matter. U-74500A co-administration was able to restore alterations in the LPO, ROS levels as well as all the three mitochondrial complexes and caspase expression. Therefore, it is suggested that 21-aminosteroids (lazaroids), by attenuating LPO and mitochondrial dysfunction, holds a promise as an agent that can potentially reduce Al-induced adverse effects in brain.

Effect of gender, biochemical parameters & parathyroid surgery on gastrointestinal manifestations of symptomatic primary hyperparathyroidism.

BACKGROUND & OBJECTIVES: Information on gastrointestinal manifestations and then response after curative parathyroid surgery is scarce in symptomatic primary hyperparathyroidism (PHPT). This study was carried out to analyse gastrointestinal manifestations in patients with PHPT and their associations with biochemical parameters. METHODS: This retrospective study included 153 patients with symptomatic primary hyperparathyroidism (PHPT). The signs and symptoms pertaining to gastrointestinal system were analyzed. The difference of symptoms between men and women and difference in biochemical parameters in presence of different symptoms were evaluated. The relationship between serum calcium, phosphate and parathyroid hormone (PTH) levels with presence of gallstone and pancreatitis was also studied. RESULT: Of the 153 patients, 46 (30%) were men. The mean age was 39.2 ± 13.9 yr. Nearly 80 per cent of PHPT patients had at least one symptom/ sign related to gastrointestinal system. The most common gastrointestinal manifestations were abdominal pain 66 (43%), constipation 55 (36%), and nausea/or vomiting 46 (30%). Nearly one-fourth 34 (22%) of patients had a history of either gallstone disease or cholecystectomy or both. The prevalence of gallstone disease was higher in women (P<0.05). Imaging and biochemical evidence of pancreatitis was found in 27 (18%) patients. Pancreatitis was more common in men compared to women (P<0.05) despite the higher prevalence of gallstones in women. Serum calcium, phosphate or PTH levels were not associated with high risk for gallstone disease, however, serum calcium (P<0.05) was associated with 1.3 times higher risk of developing pancreatitis. In majority of patients, gastrointestinal manifestations resolved within three months of curative parathyroidectomy. Except two patients, none had recurrence of pancreatitis. INTERPRETATION & CONCLUSIONS: The study revealed that the gastrointestinal symptoms were common in patients with symptomatic PHPT. There was not much gender difference in gastrointestinal symptoms except higher occurrence of gallstones in women and pancreatitis in men. There was no difference in biochemical profile between those who had and did not have gastrointestinal symptoms.

Carcinoma esophagus with small bowel metastasis: a case report with review of literature.

Small intestinal metastasis is extremely rare and only 13 cases have been reported till date and almost all such patients have presented with intestinal obstruction. The 5-year overall survival for metastatic esophageal cancer is as low as 5% while the patients with small intestinal metastasis have a median survival of only 3 months (range 1-12 months) despite undergoing radical resection of the small bowel. We present a case of a male in his 50's who presented with difficulty in swallowing for 4 months. On evaluation, he was found to have squamous cell carcinoma in the mid thoracic esophagus. He underwent radical chemo-radiation up to 60 Gy in 25 fractions over 5 weeks. One week after completion of treatment he presented with ileal obstruction and omental nodules and surgical resection and evaluation of the respective ileal segment and omental biopsy revealed a metastatic squamous cell carcinoma. The patient expired 3 months post-surgery. Carcinoma esophagus with small bowel metastasis has a very grave prognosis that patients rarely survive beyond 1 year despite undergoing resection. Hence it is imperative to consider a small bowel metastasis when such patients present with clinical features of intestinal obstruction for early diagnosis and aggressive management.

Chondroprotective Effects of a Single PRP Injection in a Spontaneous Osteoarthritis Model of Dunkin Hartley Guinea Pig: An Immunohistochemical Analysis.

Purpose of the Study: The evaluation of anti-apoptotic and chondroprotective properties of a single injection of PRP using immunohistochemistry (IHC). Methods: This was a placebo-controlled blinded experimental study. Ten healthy Dunkin Hartley guinea pigs were selected. One knee of each animal was injected with a single injection of PRP (Group A); the contralateral knee acted as a control and was injected with a single injection of normal saline (Group B). These groups were further divided into A3 and B3 based on the timeline of animal sacrifice (3 months) and A6 and B6 (6 months). The formalin-preserved articular cartilage blocks were subjected to IHC to stain Aggrecan, Caspase-3, and Collagen-2. Results: The mean IHC score was significantly low for Caspase-3 (p-0.029) in intervention group (A3) in comparison to placebo control group (B3) pointing towards decreased apoptosis. The mean IHC values were significantly higher for Collagen II (p-0.011) for intervention group (A6) in contrast to control group (B6); values were also significantly low for Caspase-3 (p-0.029) in A6 as compared to B6. The mean Caspase-3 values were significantly higher in A6 as compared to A3 (p-0.029). Conclusion: The impact of a solitary injection of PRP on upregulation of anabolic pathways inside cartilage is relatively slower as compared to its effect on downregulation of apoptotic pathways. Even a single PRP injection holds the potential to change cartilage microenvironment, but the effects are not long lasting.

Multimodality imaging of myocardial tuberculosis presenting as right ventricular cardiomyopathy: A case report.

An 18-year male with no significant past medical history presented with features of right-sided heart failure. Haematological investigations revealed raised erythrocyte sedimentation rate (23 mm/h). Transthoracic echocardiography (TTE) demonstrated biventricular systolic dysfunction with thickened free wall of right ventricle (RV). Whole-body fluorodeoxyglucose (FDG)-positron emission tomography (PET) computed tomography (FDG-PET-CT) showed intensely increased FDG uptake in the thickened RV wall and an FDG avid lesion in the left medial temporal lobe. Cardiac magnetic resonance imaging (CMR) characterized thickening and suggested an infiltrative disease (isointense on TI, hyperintense on myocardial oedema sensitive sequence with transmural enhancement on late gadolinium sequence). Magnetic resonance imaging (MRI) brain showed a thick rim enhancing ring lesion in the body of hippocampus. Endomyocardial biopsy revealed moderately dense lymphomononuclear inflammation with the formation of granulomas. Since tuberculosis is endemic in our country and considering all laboratory, imaging and biopsy findings a working diagnosis of tuberculosis was considered, and standard anti-tubercular treatment was started. There was an improvement in clinical status and follow-up imaging (TTE, CMR, brain MRI and FDG-PET-CT) showed improvement in biventricular function with regression in myocardial thickening and resolution of brain lesion, confirming the diagnosis of tuberculosis.

IL-17 A correlates with disease progression in papillary thyroid carcinoma.

BACKGROUND: Cancer progression can be promoted by chronic inflammation. Local immune response may be associated with favourable or unfavourable prognosis of Papillary Thyroid Carcinoma (PTC). Regulatory T (Treg) cells and T helper 17 (Th17) cells exert opposing function and their balance may have a vital role in promotion of tumor growth. Treg cells in tumor microenvironment (TME) may promote tumor progression and reduced survival of patients. Whereas, Th17 cells can promote or inhibit tumor progression depending on phenotypic characteristics of tumor. In this study, we aimed to analyse the kind of immune response developed and its prognostic impact in future therapeutics. METHODS: Cytometric Bead Array (CBA) analysis of pro and anti-inflammatory cytokines (IFN-gamma, IL-2, IL-6, IL-17 A, TNF-alpha and IL-4, IL-10) was done in 15 PTC irrespective of Lymphocytic Thyroiditis (LT) and 16 Hashimoto's Thyroiditis (HT) cases. Immunohistochemical expression of FoxP3 and IL-17 A was studied in 27 cases of PTC with LT. Whereas, quantitative gene expression of both was analysed in 10 cases. RESULTS: All the pro-inflammatory cytokines showed mild elevation in PTC with LT. On IHC, IL-17 A expression was observed in 74% PTC with LT. Whereas, FoxP3 was present in only 40% cases. Also, IL-17 A expression was significantly associated with age group (> 45 years), tumor size ≤ 1 cm and disease progression. CONCLUSIONS: Increased expression of cytokines suggested correlation between inflammatory factors and progression of thyroid tumors. Along with this, the balance between IL-17 A and FoxP3 may play an important role in PTC development, prognosis and future management.

Stress proteins and glial cell functions during chronic aluminium exposures: protective role of curcumin.

Involved in the ongoing debate is the speculation that aluminium is somehow toxic for neurons. Glial cells cope up to protect neurons from this toxic insult by maintaining the glutathione homeostasis. Of late newer and newer roles of glial cells have been depicted. The present work looks into the other regulatory mechanisms that show the glial cells response to pro-oxidant effects of aluminium exposure. In the present investigation we have evaluated the inflammatory responses of the glial cells as well as HSP70-induction during aluminium exposure. Further, the protective role of curcumin is also evaluated. Aluminium was administered by oral gavage at a dose level of 100 mg/kg b.wt/day for a period of 8 weeks. Curcumin was administered i.p. at a dose of 50 mg/kg b.wt./day on alternate days. Enhanced gene and protein expression of HSP70 in the glial fractions of the aluminium exposed animals as compared to the corresponding neuronal population. Aluminium exposure resulted in a significant increase in the NF-κB and TNF-α expression suggesting inflammatory responses. In the conjunctive treatment group of aluminium and curcumin exposure marked reduction in the gene and protein expression of NF-κB and TNF-α was observed. This was further reflected in histopathological studies showing no evidence of inflammation in conjunctive group as compared to aluminium treatment. From the present study, it can be concluded that curcumin has a potential anti-inflammatory action and can be exploited in other toxicological conditions also.

Adrenal histoplasmosis: unusual presentations.

BACKGROUND: Histoplasmosis has been sporadically reported from India. Though asymptomatic adrenal involvement has been described in patients with disseminated histoplasmosis; isolated adrenal involvement with adrenal insufficiency (AI) as the presenting manifestation of the disease is rare. PATIENTS AND METHODS: We describe 5 immunocompetent men (mean age 55.6 yrs) from a nonendemic area with adrenal histoplasmosis presenting with constitutional symptoms. Three patients had AI at presentation with bilateral adrenal involvement and the other two developed AI during the course of the illness and had unilateral adrenal mass . All the patients had histopathological/cytologically proven adrenal histoplasmosis. 18FDG-PET done in 3 patients helped in delineating the extent of the disease. Adrenalectomy was done in 2 patients who presented with unilateral adrenal mass. All these patients received Amphotericin B and/or itraconazole treatment which led to symptomatic improvement but AI persisted in all at the end of the follow up of 6 to 18 months. CONCLUSION: The diagnosis of adrenal histoplasmosis should be considered in patients presenting with constitutional symptoms and unilateral or bilateral adrenal mass/es with or without AI.

Invasive cardiac aspergillosis as contiguous infiltration from mediastinum: Imaging evaluation using cardiac MRI.

Invasive cardiac aspergillosis is a rare, potentially fatal disease which poses a significant diagnostic challenge. Combination of clinical details, imaging features, fungal markers, serology and fungal isolation with demonstration of invasion is usually necessary to establish the diagnosis. High index of suspicion is the key for early diagnosis with potential role of cardiac MRI in its early detection, delineation of extent of involvement and guidance to the appropriate site for tissue sampling, thereby allowing for improved prognosis with early institution of appropriate therapy.

Chondroprotective effects of multiple PRP injections in osteoarthritis by apoptosis regulation and increased aggrecan synthesis- Immunohistochemistry based Guinea pig study.

OBJECTIVE: Use of Immunohistochemistry as a tool to assess anti-apoptotic effects and cartilage regeneration effects of PRP in guinea pig model of spontaneous OA. STUDY DESIGN: Controlled Laboratory Study involving Dunkin-Hartley guinea pigs. METHODS: 12 Dunkin-Hartley guinea pigs (weighing ∼600-800 g) were chosen for this study. One knee of each animal received 3 injections of allogenic PRP at weekly intervals (Group A = 12 Knees). The other knee received normal saline and acted as the control group (Group B = 12 Knees). Half of the animals from each group (subgroups A3 & B3 = 6 Knees each) were sacrificed at 3 months, and the remaining half (subgroups A6 & B6 = 6 Knees each) were sacrificed at 6 months after intervention. Immunohistochemistry (IHC) staining and evaluation were done for Collagen-II, Caspase-3 and Aggrecan. RESULTS: The mean IHC score for Caspase-3 were significantly low in PRP knees compared to placebo Knees at 3 months (P = 0.031) and 6 months (P = 0.012) suggesting its down-regulation and inhibition of apoptosis. The mean IHC score for content of collagen- II and aggrecan at 3 months were higher in PRP Knees (A3) compared to placebo (B3) (Not significant). At 6 months, the Mean IHC Score decreased in both PRP (A6) and Control Knees (B6) for Collagen, but increased for aggrecan compared to its value at 3 months; and this was better in PRP group than in the control (P = 0.024). CONCLUSION: Multiple injections of PRP has a chondroprotective role by its anti-apoptotic effect and by increasing the aggrecan content in ECM.

Role of cytotoxic T cells and PD-1 immune checkpoint pathway in papillary thyroid carcinoma.

Background: Lymphocytic thyroiditis (LT) is frequently seen in the tumor microenvironment (TME) of papillary thyroid carcinomas (PTCs). However, the characteristic of these tumor-infiltrating lymphocytes (TILs) is not well understood. Objective: We aim to define the TME of PTC cases by characterizing the TILs. Design: This is a cross-sectional observational study. Patients: We enrolled 29 PTC (23 having concurrent LT), 14 LT, and 13 hyperplastic nodules with LT (HN) patients from January 2016 to December 2020. Measurements: Immunohistochemical (IHC) expression of CD8, FoxP3, PD-1, and PD-L1 was studied in PTC with LT and compared with HN. PD-1 and PD-L1 expression was correlated at the mRNA level by quantitative real-time PCR. Immunophenotyping of TILs was done in FNAC samples of PTC and LT by flow cytometry. Results: IHC revealed the presence of CD8+ cytotoxic T lymphocytes (CTLs) and FoxP3+ T regulatory cells (Tregs) in 83% and 52% of PTC with LT cases, respectively. Flow cytometric analysis of the PTC samples revealed a significant abundance of CTL compared with Treg and a higher CTL with lower Treg counts compared with LT. On IHC, PD-1 positivity was noted in 56.5% of PTC with LT cases, while intermediate PD-L1 positivity was found in 70% of the cases. There was a significant upregulation of PD-1 mRNA in PTC with LT. A significant correlation was noted with PD-L1 expression with lymph node metastasis and presence of Treg cells. Conclusions: Increased expression of PD-1 and PD-L1 in the TME of PTC may provide a potential molecular mechanism for tumor survival despite the predominance of CTLs, possibly through their inactivation or exhaustion.

Fibrous dysplasia & McCune-Albright syndrome: an experience from a tertiary care centre in north India.

BACKGROUND & OBJECTIVES: Fibrous dysplasia (FD) is a rare metabolic bone disease and information available from India is limited to only anecdotal case reports. We describe the clinical profile and therapeutic outcome of 25 patients with FD observed over a period of 14 yr in a tertiary care centre from north India. METHODS: In this retrospective study patients (n = 25) with diagnosis of fibrous dysplasia based on either classical radiological features and/or histological evidence on bone biopsy, were analyzed. Associated endocrinopathies if any, were evaluated. The diagnosis of McCune Albright syndrome (MAS) was considered when fibrous dysplasia was accompanied by either café-au-lait macules and/or endocrinopathies. The clinical presentation, biochemical parameters and imaging were analysed. Seven patients received bisphosphonate therapy. The final outcome and side effects were noted. RESULTS: Age of the patients ranged from 7 to 48 yr (mean ± SD, 24.2 ± 11.4 yr) with a lag time between onset of symptoms and presentation ranging from 1 to 20 yr (mean ± SD, 6.6 ± 6.2 yr). The mean duration of follow up was 3.5 ± 2.1 yr. Eighteen (72%) patients had polyostotic disease while the remaining had monostotic FD. Eight patients had endocrinopathies: five had acromegaly, one each had gonadotropin independent precocious puberty (GIPP), hyperthyroidism and hypophosphatemic rickets. One child with GIPP later developed hyperthyroidism. McCune Albright syndrome was observed in 10 (40%) patients. A majority of the patients underwent various minor or major surgical procedures and seven patients received bisphosphonates for recurrent pathological fractures. Bone pain was reduced in all bisphosphonate treated patients with a decrease in subsequent fractures. INTERPRETATION & CONCLUSIONS: This series of FD patients from north India shows the varying presentations of this rare disease. Medical treatment with bisphosphonates appears to be potentially rewarding.

Surgical outcome after focused parathyroidectomy: experience from a tertiary care centre in North India.

<b style="color: #075541"> Introduction:</b> Focused parathyroidectomy is the gold standard treatment for primary hyperparathyroidism (PHPT) due to single gland disease with a comparable success rate as that of conventional four gland exploration. It is also associated with fewer surgical complications. Despite these benefits, there is still controversy about the high recurrence following the focused approach. </br> </br> <b style="color: #075541">Aim:</b> The aim was to analyse our experience regarding the success rate of focused parathyroidectomy for PHPT. </br> </br> <b style="color: #075541">Methods:</b> This was a retrospective analysis of 192 patients of PHPT between January 2017 and August 2020 who underwent focused parathyroidectomy without intraoperative parathormone analysis, and had a minimum follow up of six months. Demographic profile, biochemical (pre and postoperative), radiological, operative and histological detail of all patients were recorded. Parathyroidectomy was considered curative if the patient maintained normal serum calcium and parathormone (PTH) levels six months after surgery. Persistent hyperparathyroidism was considered if hypercalcemia or high PTH levels persisted, or recurrent disease when a patient had rising serum calcium and / or PTH levels six months after curative parathyroidectomy. </br> </br> <b style="color: #075541">Results:</b> No patient had pain and wound-related complications after parathyroidectomy. Two patients had voice change in the immediate postoperative period which recovered subsequently; no patient had documented vocal cord paralysis. The persistent disease was present in two patients; both required neck exploration. Five patients had recurrence of PHPT within six months of parathyroidectomy; all of them had hyperplasia on the final biopsy. The overall cure rate was 97.92%. </br> </br> <b style="color: #075541">Conclusion:</b> Therefore, we propose focused surgery for sporadic PHPT should be considered as a preferred treatment with acceptable recurrence rate and surgical complications.</br> </br> <b style="color: #075541">KEYWORDS:</b>focused parathyroidectomy, parathyroidectomy, primary hyperparathyroidism.

Neuroprotective effect of bone marrow-derived mesenchymal stem cell secretome in 6-OHDA-induced Parkinson's disease.

Aim: The aim of the study was to evaluate the neuroprotective effect of bone marrow stem cell secretome in the 6-hydroxydopamine (6-OHDA) model of Parkinson's disease. Materials & methods: Secretome prepared from mesenchymal stem cells of 3-month-old rats was injected daily for 7 days between days 7 and 14 after 6-OHDA administration. After 14 days, various neurobehavioral parameters were conducted. These behavioral parameters were further correlated with biochemical and molecular findings. Results & conclusion: Impaired neurobehavioral parameters and increased inflammatory, oxidative stress and apoptotic markers in the 6-OHDA group were significantly modulated by secretome-treated rats. In conclusion, mesenchymal stem cell-derived secretome could be further explored for the management of Parkinson's disease.

Molecular Imaging Targeting Corticotropin-releasing Hormone Receptor for Corticotropinoma: A Changing Paradigm.

BACKGROUND: Corticotrophin-releasing hormone (CRH) is the major regulator of adrenocorticotrophic hormone (ACTH) secretion from the anterior pituitary and acts via CRH-1 receptors (CRH-1R). Corticotropinoma though autonomous, still retain their responsiveness to CRH and hence, we hypothesize that in vivo detection of CRH-1 receptors on pituitary adenoma using Gallium-68 (68Ga)-tagged CRH can indicate the functionality of adenoma, and combining it with positron emission tomography-computed tomography (PET-CT) can provide requisite anatomical information. METHODS: Subjects with ACTH-dependent Cushing's syndrome (CS) (n = 27, 24 with Cushing's disease [CD], 3 with ectopic CS [ECS]) underwent 68Ga CRH PET-CT. Two nuclear medicine physicians read these images for adenoma delineation and superimposed them on magnetic resonance imaging (MRI) sella. The information provided was used for intraoperative navigation and compared with operative and histopathological findings. FINDINGS: 68Ga CRH PET-CT correctly delineated corticotropinoma in all the 24 cases of CD, including the 10 cases with adenoma size < 6mm (4 cases were negative on MRI). Corticotropinoma location on 68Ga CRH PET fusion images with MRI were concordant with operative findings and were further confirmed on histopathology. There was no tracer uptake in the pituitary in 2 patients with ECS, while, in another, the diffuse uptake in pituitary suggested ectopic CRH production. CONCLUSION: 68Ga CRH PET-CT represents a novel, noninvasive molecular imaging, targeting CRH receptors that not only delineate corticotropinoma and provides the surgeon with valuable information for intraoperative tumor navigation, but also helps in differentiating a pituitary from an extra-pituitary source of ACTH-dependent CS. FUNDING: None.