Pattern of preventable diseases in Afghanistan: suggestions to reduce the morbidity and mortality at IGICH

Over nine years period (1354-1362), 1,39,436 children were admitted in Indira Gandhi Institute of Child Health (IGICH), Kabul. Of these 51,212 (46.8%) children were hospitalised with preventable diseases. Seventy four per cent of patients were under five years of age. Among the infectious diseases, gastroenteritis accounted for nearly 70% of admissions. Tuberculosis, measles, diphtheria and typhoid fever were other common infectious diseases. Malnutrition of varying degree was the core problem among the hospitalised children and was seen in nearly two thirds of admissions. Twenty per cent of them had severe protein energy malnutrition which contributed for higher mortality. Gastroenteritis contributed for half (51.5%) of the mortality. Septicemia, tetanus neonatorum and central nervous system infections were associated with high mortality especially among the neonates. Deaths following 6-target preventable diseases accounted for nearly 1/4th of deaths (20.4-24.6%) over these years.     

Comparison of Local Measurement of Cerebral Metabolism and to Cerebral PvO2 during Alterations in Intracranial Pressure, PaCO2 and Arterial Pressure – An Experimental Study in Goat

Objective.to assess the changes in local brain PO₂, PCO₂, pH (PO₂br, PCO₂br, pHbr) measured by a intraparenchymal probe (Neurotrend^TM, Codeman) and compare them to simultaneous recording of cerebral PvO₂ and blood flow (CBF). Methods.Arterial, venous longitudinal sinus blood samples and CBF were analyzed in 8 adult anesthetized, ventilated goats. Three step increase of intracranial pressure (ICP) (16, 22, 29 mm Hg) were performed by inflation of an epidural balloon. At each ICP level, similar changes in MAP and in PaCO₂ were performed. Results.At constant PaCO₂ and MAP, balloon inflation induced a fast response: a decrease of PO₂br, PCO₂br and pHbr (starting 14 ± 12 sec, 45 ± 23 sec and 55 ± 19 sec after the peak ICP, respectively). Since the second inflation level, PO₂br decreased (p< 0.05) despite an ICP returning at 22 mm Hg and a cerebral perfusion pressure (CPP) larger than 90 mmHg. During changes in PaCO₂, PO₂br paralleled CBF and PvO₂ before the second balloon inflation but diverged at higher ICP. In the same time pH-pHbr gradient rose. Hypotension did not induce sizeable changes. Conclusions.The direct metabolic monitoring of cerebral tissue locally compressed show fast response. At steady state, it shows alterations which are not detected by the measurement of the oxygen saturation in the longitudinal sinus or that of CBF. It confirms that the threshold for ICP which may require therapy in presence of focal brain compression is around 20 mm Hg even in the presence of a CPP > 90 mm Hg.     

Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

Purpose

The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer.

Procedures

CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated in a xenograft breast cancer mouse model using ductal carcinoma in situ cells (DCIS).

Results

Specific anti-CAIX nanobodies were obtained. Administration of a CAIX-specific nanobody into mice with DCIS xenografts overexpressing CAIX showed after 2 h a mean tumor-to-normal tissue ratio (TNR) of 4.3?±?0.6, compared to a TNR of 1.4?±?0.2 in mice injected with the negative control nanobody R2-IR. In DCIS mice, a TNR of 1.8?±?0.1 was obtained. Biodistribution studies demonstrated an uptake of 14.0?±?1.1 %I.D./g in DCIS?+?CAIX tumors, 4.6?±?0.8 %I.D./g in DCIS tumors, while 2.0?±?0.2 %I.D./g was obtained with R2-IR.

Conclusions

These results demonstrate the successful generation of a CAIX-specific nanobody-IRDye800CW conjugate that can be used for rapid imaging of (pre-)invasive breast cancer.

     

Nortriptyline influences protein pathways involved in carbohydrate metabolism and actin-related processes in a rat gene-environment model of depression

Although most available antidepressants increase monoaminergic neurotransmission, their therapeutic efficacy is likely mediated by longer-term molecular adaptations. To investigate the molecular changes induced by chronic antidepressant treatment we analysed proteomic changes in rat pre-frontal/frontal cortex and hippocampus after nortriptyline (NT) administration. A wide-scale analysis of protein expression was performed on the Flinders Sensitive Line (FSL), a genetically-selected rat model of depression, and the control Flinders Resistant Line (FRL). The effect of NT treatment was examined in a gene-environment interaction model, applying maternal separation (MS) to both strains.In the forced swim test, FSL rats were significantly more immobile than FRL animals, whereas NT treatment reduced immobility time. MS alone did not modify immobility time, but it impaired the response to NT in the FSL strain.In the proteomic analysis, in FSL rats NT treatment chiefly modulated cytoskeleton proteins and carbohydrate metabolism. In the FRL strain, changes influenced protein polymerization and intracellular transport. After MS, NT treatment mainly affected proteins in nucleotide metabolism in FSL rats and synaptic transmission and neurite morphogenesis pathways in FRL rats. When the effects of NT treatment and MS were compared between strains, carbohydrate metabolic pathways were predominantly modulated.     

Acute stress differentially affects corticotropin-releasing hormone mRNA expression in the central amygdala of the "depressed" flinders sensitive line and the control flinders resistant line rats

Preclinical and clinical evidence suggests that neuropeptides play a role in the pathophysiology of mood disorders. In the present study, we investigated the involvement of the peptides corticotropin-releasing hormone (CRH), neuropeptide Y (NPY) and nociceptin/orphanin FQ (N/OFQ) and of their receptors in the regulation of emotional behaviours. In situ hybridization experiments were performed in order to evaluate the mRNA expression levels of these neuropeptidergic systems in limbic and limbic-related brain regions of the Flinders Sensitive Line (FSL) rats, a putative genetic animal model of depression. The FSL and their controls, the Flinders Resistant Line (FRL) rats, were subjected to one hour acute restraint and the effects of the stress exposure, including possible strain specific changes on these neuropeptidergic systems, were studied. In basal conditions, no significant differences between FSL and FRL rats in the CRH mRNA expression were found, however an upregulation of the CRH mRNA hybridization signal was detected in the central amygdala of the stressed FRL, compared to the non stressed FRL rats, but not in the FSL, suggesting a hypoactive mechanism of response to stressful stimuli in the "depressed" FSL rats. Baseline levels of NPY and N/OFQ mRNA were lower in the FSL rats compared to the FRL in the dentate gyrus of hippocampus and in the medial amygdala, respectively. However, the exposure to stress induced a significant upregulation of the N/OFQ mRNA levels in the paraventricular thalamic nucleus, while in the same nucleus the N/OFQ receptor mRNA expression was higher in the FSL rats. In conclusion, selective alterations of the NPY and N/OFQ mRNA in limbic and limbic-related regions of the FSL rats, a putative animal model of depression, provide further support for the involvement of these neuropeptides in depressive disorders. Moreover, the lack of CRH activation following stress in the "depressed" FSL rats suggests a form of allostatic load, that could alter their interpretation of environmental stimuli and influence their behavioural response to stressful situations.