The question concerning human rights and human rightlessness: disposability and struggle in the Bhopal gas disaster

In the midst of concerns about diminishing political support for human rights, individuals and groups across the globe continue to invoke them in their diverse struggles against oppression and injustice. Yet both those concerned with the future of human rights and those who champion rights activism as essential to resistance, assume that human rights – as law, discourse and practices of rights claiming – can ameliorate rightlessness. In questioning this assumption, this article seeks also to reconceptualise rightlessness by engaging with contemporary discussions of disposability and social abandonment in an attempt to be attentive to forms of rightlessness co-emergent with the operations of global capital. Developing a heuristic analytics of rightlessness, it evaluates the relatively recent attempts to mobilise human rights as a frame for analysis and action in the campaigns for justice following the 3 December 1984 gas leak from Union Carbide Corporation’s (UCC) pesticide manufacturing plant in Bhopal, India. Informed by the complex effects of human rights in the amelioration of rightlessness, the article calls for reconstituting human rights as an optics of rightlessness

Valeric Acid Protects Dopaminergic Neurons by Suppressing Oxidative Stress, Neuroinflammation and Modulating Autophagy Pathways

Parkinson’s disease, the second common neurodegenerative disease is clinically characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) with upregulation of neuroinflammatory markers and oxidative stress. Autophagy lysosome pathway (ALP) plays a major role in degradation of damaged organelles and proteins for energy balance and intracellular homeostasis. However, dysfunction of ALP results in impairment of α-synuclein clearance which hastens dopaminergic neurons loss. In this study, we wanted to understand the neuroprotective efficacy of Val in rotenone induced PD rat model. Animals received intraperitoneal injections (2.5 mg/kg) of rotenone daily followed by Val (40 mg/kg, i.p) for four weeks. Valeric acid, a straight chain alkyl carboxylic acid found naturally in Valeriana officianilis have been used in the treatment of neurological disorders. However, their neuroprotective efficacy has not yet been studied. In our study, we found that Val prevented rotenone induced upregulation of pro-inflammatory cytokine oxidative stress, and α-synuclein expression with subsequent increase in vital antioxidant enzymes. Moreover, Val mitigated rotenone induced hyperactivation of microglia and astrocytes. These protective mechanisms prevented rotenone induced dopaminergic neuron loss in SNpc and neuronal fibers in the striatum. Additionally, Val treatment prevented rotenone blocked mTOR-mediated p70S6K pathway as well as apoptosis. Moreover, Val prevented rotenone mediated autophagic vacuole accumulation and increased lysosomal degradation. Hence, Val could be further developed as a potential therapeutic candidate for treatment of PD

Myrcene Salvages Rotenone-Induced Loss of Dopaminergic Neurons by Inhibiting Oxidative Stress, Inflammation, Apoptosis, and Autophagy

Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, resulting in motor deficits. The exact etiology of PD is currently unknown; however, the pathological hallmarks of PD include excessive production of reactive oxygen species, enhanced neuroinflammation, and overproduction of α-synuclein. Under normal physiological conditions, aggregated α-synuclein is degraded via the autophagy lysosomal pathway. However, impairment of the autophagy lysosomal pathway results in α-synuclein accumulation, thereby facilitating the pathogenesis of PD. Current medications only manage the symptoms, but are unable to delay, prevent, or cure the disease. Collectively, oxidative stress, inflammation, apoptosis, and autophagy play crucial roles in PD; therefore, there is an enormous interest in exploring novel bioactive agents of natural origin for their protective roles in PD. The present study evaluated the role of myrcene, a monoterpene, in preventing the loss of dopaminergic neurons in a rotenone (ROT)-induced rodent model of PD, and elucidated the underlying mechanisms. Myrcene was administered at a dose of 50 mg/kg, 30 min prior to the intraperitoneal injections of ROT (2.5 mg/kg). Administration of ROT caused a considerable loss of dopaminergic neurons, subsequent to a significant reduction in the antioxidant defense systems, increased lipid peroxidation, and activation of microglia and astrocytes, along with the production of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β) and matrix metalloproteinase-9. Rotenone also resulted in impairment of the autophagy lysosomal pathway, as evidenced by increased expression of LC3, p62, and beclin-1 with decreased expression in the phosphorylation of mTOR protein. Collectively, these factors result in the loss of dopaminergic neurons. However, myrcene treatment has been observed to restore antioxidant defenses and attenuate the increase in concentrations of lipid peroxidation products, pro-inflammatory cytokines, diminished microglia, and astrocyte activation. Myrcene treatment also enhanced the phosphorylation of mTOR, reinstated neuronal homeostasis, restored autophagy-lysosomal degradation, and prevented the increased expression of α-synuclein following the rescue of dopaminergic neurons. Taken together, our study clearly revealed the mitigating effect of myrcene on dopaminergic neuronal loss, attributed to its potent antioxidant, anti-inflammatory, and anti-apoptotic properties, and favorable modulation of autophagic flux. This study suggests that myrcene may be a potential candidate for therapeutic benefits in PD

Lycopodium Attenuates Loss of Dopaminergic Neurons by Suppressing Oxidative Stress and Neuroinflammation in a Rat Model of Parkinson’s Disease

Parkinson’s disease, a chronic, age related neurodegenerative disorder, is characterized by a progressive loss of nigrostriatal dopaminergic neurons. Several studies have proven that the activation of glial cells, presence of alpha-synuclein aggregates, and oxidative stress, fuels neurodegeneration, and currently there is no definitive treatment for PD. In this study, a rotenone-induced rat model of PD was used to understand the neuroprotective potential of Lycopodium (Lyc), a commonly-used potent herbal medicine. Immunohistochemcial data showed that rotenone injections significantly increased the loss of dopaminergic neurons in the substantia nigra, and decreased the striatal expression of tyrosine hydroxylase. Further, rotenone administration activated microglia and astroglia, which in turn upregulated the expression of α-synuclein, pro-inflammatory, and oxidative stress factors, resulting in PD pathology. However, rotenone-injected rats that were orally treated with lycopodium (50 mg/kg) were protected against dopaminergic neuronal loss by diminishing the expression of matrix metalloproteinase-3 (MMP-3) and MMP-9, as well as reduced activation of microglia and astrocytes. This neuroprotective mechanism not only involves reduction in pro-inflammatory response and α-synuclein expression, but also synergistically enhanced antioxidant defense system by virtue of the drug’s multimodal action. These findings suggest that Lyc has the potential to be further developed as a therapeutic candidate for PD

⁶⁸Ga-DOTA-TATE PET vs. ¹²³I-MIBG in identifying malignant neural crest tumours

Purpose: We aimed to compare imaging with ¹²³I-MIBG and ⁶⁸Ga-DOTA-TATE in neural crest tumours (NCT) to see if the latter could offer more advantage in detecting extra lesions and have higher sensitivity for malignant lesions. Procedures: We retrospectively reviewed 12 patients (M=10, F=2; age range 20-71 years) with NCT (phaeochromocytomas = 7, paragangliomas = 4, medullary thyroid cancer = 1) who underwent both ⁶⁸Ga-DOTA-TATE positron emission tomography (PET) or PET/computed tomography (CT) and ¹²³IMIBG single-photon emission computed tomography within 6months. Visual assessment of all lesions and measurement of target/non-target (T/N) ratio in selected lesions were performed. Five patients (aged 50 or less) had SDHB screening results correlated with imaging results of both radiopharmaceuticals. All patients had contrast-enhanced CT and/or other cross-sectional imaging. Results: ⁶⁸Ga-DOTA-TATE PET showed tumour lesions in ten out of 12 patients with confirmed disease, while ¹²³I-MIBG showed lesions in five out of 12 patients. In one patient, both ⁶⁸Ga-DOTATATE PET and ¹²³I-MIBG were negative, but CT, magnetic resonance imaging, and 2-deoxy-2-[¹⁸F] fluoro-D-glucose PET scans identified a lesion in the thorax. ⁶⁸Ga-DOTA-TATE and ¹²³I-MIBG detected a total of 30 lesions, of which 29/30 were positive with ⁶⁸Ga-DOTA-TATE and 7/30 with ¹²³I-MIBG. We also found higher incidence of SDHB positive results in patients with positive ⁶⁸Ga-DOTA-TATE. Conclusion: Our limited data suggest that ⁶⁸Ga-DOTA-TATE is a better imaging agent for NCT and detects significantly more lesions with higher T/Nratio compared to ¹²³I- MIBG. ⁶⁸Ga-DOTA-TATE was more likely to detect malignant lesions as indicated by correlating imaging results with SDHB screening.7 page(s

Clinical characteristics of functioning gonadotroph adenoma in women presenting with ovarian hyperstimulation: audit of UK pituitary centres.

Objective Functioning gonadotroph adenomas (FGAs) are rare pituitary tumours stimulating ovarian function with potential life-threatening consequences in women. However, a lack of aggregated clinical experience of FGAs impairs management in affected women. The aim of this study is to present the clinical course of FGA-induced ovarian hyperstimulation syndrome (OHSS) cases as identified by some of the largest UK pituitary endocrine tertiary centres with a view to increasing awareness and improving diagnosis and management of women with FGA. Design A retrospective observational study; audit of eight UK regional pituitary centres for cases of FGAs. Setting Specialist neuroendocrine centres in the United Kingdom. Patients and Measurements Women diagnosed with FGA-induced OHSS. Description of their clinical course. Results Seven cases of FGA were identified in women, all causing OHSS. Mean age was 33.4 years at diagnosis. Abdominal pain, irregular periods, headache, and visual disturbances were reported at presentation by 100%, 71%, 57% and 43% of women, respectively. Three of seven women underwent ovarian surgery before FGA diagnosis. Six women underwent transsphenoidal surgery (TSS) with incomplete tumour resection in five of those, but all showed improvement or resolution in symptoms and biochemistry postoperatively. Conclusion FGA is a rare cause of spontaneous OHSS. TSS improves clinical and biochemical features of ovarian hyperstimulation in FGAs. Improved awareness of FGA will prevent inappropriate emergency ovarian surgery