Sulpiride in negative schizophrenia: A placebo-controlled double-blind assessment

Twenty-four chronic schizophrenic long-stay hospital patients were identified, who had not received neuroleptic drugs for 8–30 (average 8 months) and met or exceeded a minimum criterion of severity of negative symptoms. They were rendomly alocated to either sulpiride 200 mg twice daily or matching placebo, on a double-blind basis for 12 weeks. The results showed that low-dose sulpiride was significantly better than placebo in relation to improvements in negative symptoms. The changes in social behaviour were complex and not obviously related to symptom improvement; exhibited abnormal behaviour, a major factor in preventing successful return to the community, consistently improved only on the active drug.     

A Quick and Easy Approach to Prepare Ground Bone Slides from Undecalcified Skeleton

Ground bone slides are not only necessary for teaching histology of Haversian system to undergraduate and postgraduate students, but also essential for rapid pathological diagnosis in related diseases as well as to be used in polarizing microscopy and studying bone architectures from fossils. This technique is also applicable for hard tissues like teeth. Present histology manual-cum-practical literatures though prefer bone-slide preparation from decalcified skeleton, but Haversian architectures with osteons are vivid in ground bone slides. Here a technique is briefed; which have practiced well to prepare the ground bone slides with very simple, cheap and easily available equipments in a very short time, which can be adopted by anatomists, odontologists and geologists for quick making of compact bone slides without hampering the bone continuity avoiding hazardous and time consuming methods or costly equipments like freezing microtome.     

On the evolution of chaperones and cochaperones and the expansion of proteomes across the Tree of Life

Across the Tree of Life (ToL), the complexity of proteomes varies widely. Our systematic analysis depicts that from the simplest archaea to mammals, the total number of proteins per proteome expanded ∼200-fold. Individual proteins also became larger, and multidomain proteins expanded ∼50-fold. Apart from duplication and divergence of existing proteins, completely new proteins were born. Along the ToL, the number of different folds expanded ∼5-fold and fold combinations ∼20-fold. Proteins prone to misfolding and aggregation, such as repeat and beta-rich proteins, proliferated ∼600-fold and, accordingly, proteins predicted as aggregation-prone became 6-fold more frequent in mammalian compared with bacterial proteomes. To control the quality of these expanding proteomes, core chaperones, ranging from heat shock proteins 20 (HSP20s) that prevent aggregation to HSP60, HSP70, HSP90, and HSP100 acting as adenosine triphosphate (ATP)-fueled unfolding and refolding machines, also evolved. However, these core chaperones were already available in prokaryotes, and they comprise ∼0.3% of all genes from archaea to mammals. This challenge—roughly the same number of core chaperones supporting a massive expansion of proteomes—was met by 1) elevation of messenger RNA (mRNA) and protein abundances of the ancient generalist core chaperones in the cell, and 2) continuous emergence of new substrate-binding and nucleotide-exchange factor cochaperones that function cooperatively with core chaperones as a network.

All cellular life is thought to have stemmed from the last universal common ancestor (LUCA) (1, 2), that emerged more than 3.6 billion y ago. Two major kingdoms of life diverged from LUCA: bacteria and archaea, which about 2 billion y later merged into the eukaryotes (3). Since the beginning of biological evolution, life’s volume has increased on a grand scale: The average size of individual cells has increased ∼100-fold from prokaryotes to eukaryotes (4), the number of cell types has increased ∼200-fold from unicellular eukaryotes to humans (5), and average body size has increased ∼5,000-fold from the simplest sponges to blue whales (6).This expansion in organismal complexity and variability was accompanied by an expansion in life’s molecular workforce, proteomes in particular, which in turn presented a challenge of reaching and maintaining properly folded and functional proteomes. Most proteins must fold to their native structure in order to function, and their folding is largely imprinted in their primary amino acid sequence (7–9). However, many proteins, and especially large multidomain polypeptides, or certain protein types such as all-beta or repeat proteins, tend to misfold and aggregate into inactive species that may also be toxic (10). Life met this challenge by evolving molecular chaperones that can minimize protein misfolding and aggregation, even under stressful out-of-equilibrium conditions favoring aggregation (11, 12). Chaperones can be broadly divided into core and cochaperones. Core chaperones can function on their own, and include ATPases heat shock protein 60 (HSP60), HSP70, HSP100, and HSP90 and the adenosine triphosphate (ATP)-independent HSP20. The basal protein holding, unfolding, and refolding activities of the core chaperones are facilitated and modulated by a range of cochaperones such as J-domain proteins (13–15).Starting from LUCA, as proteomes expanded, so did the core chaperones and their respective cochaperones. Indeed, chaperones have been shown to facilitate the acquisition of destabilizing mutations and thereby accelerate protein evolution (16–18). However, the coexpansion of proteomes and of chaperones, underscoring a critical balance between evolutionary innovation and foldability, remains largely unexplored. We thus embarked on a systematic bioinformatics analysis that explores the evolution of both proteomes and chaperones, and of both core and their auxiliary cochaperones, along the Tree of Life.     

Are There Age Differences in Consolidated Episodic Memory?

Background/Study Context: While most aging research on memory uses a retention interval of one hour or less, episodic consolidation takes longer (e.g., 6–24 hours for synaptic consolidation). In three experiments, we examined age differences in recall followed by recognition in which the retention interval was varied in younger and older adults.

Methods: In Experiment 1 (n = 24 for both age groups), zero-, 1- and 24-hour retention intervals were used for recall for all participants, and a 24-hour retention interval was used for recognition. In Experiment 2 (n = 24 for both age groups), just a 24-hour retention interval was used. In Experiment 3 (n = 20 for both age groups), a within-subjects design was used in which participants recalled one word list after one hour and again after 24 hours, and recalled another word list just after 24 hours (with recognition for both conditions after the 24-hour recall).

Results: In Experiment 1, older adults recalled fewer words at both the 1- and 24-hour retention intervals, but the magnitude of the age difference did not differ. In Experiment 2 (just 24-hour retention interval), there were no age differences in recall. In Experiment 3, in the two-recall condition, older adults showed lower recall at both 1-hour and 24-hour retention intervals (but the magnitude of the age difference remained constant across retention interval). In the single-recall just 24-hour retention condition, there were no age differences. There were no age differences in recognition in any of the three experiments.

Conclusion: These results suggest that recall declines for a 24-hour retention interval relative to a zero or one-hour retention interval (Experiments 1 and 3) for both age groups. However, when the first recall attempt occurs after a 24-hour retention interval, there are no age differences. These replicated results suggest that older adults do not benefit as much as younger adults from pre-consolidated rehearsal, but that rehearsal-based age differences do not increase in magnitude from the last rehearsal to memory consolidation. Furthermore, (along with), the present results indicate that there are no age differences in recall when the first recall attempt occurs after a long retention interval – when memory consolidation is likely to have occurred before the first retrieval attempt.     

Increased levels of interleukin-10 and IgG3 are hallmarks of Indian post-kala-azar dermal leishmaniasis

BACKGROUND: Post-kala-azar dermal leishmaniasis (PKDL), an established sequela of visceral leishmaniasis (VL), is proposed to facilitate anthroponotic transmission of VL, especially during interepidemic periods. Immunopathological mechanisms responsible for Indian PKDL are still poorly defined. METHODS: Our study attempted to characterize the immune profiles of patients with PKDL or VL relative to that of healthy control subjects by immunophenotyping, intracellular cytokine staining of peripheral blood mononuclear cells, and enzyme-linked immunosorbent assay for serum cytokines and immunoglobulin G (IgG) subclasses. RESULTS: Patients with PKDL had significantly raised percentages of peripheral CD3+CD8+ cells compared with control subjects, a difference that persisted after cure. Patients with PKDL showed an intact response to phytohemagglutinin, with the percentages of lymphocytes expressing interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10 being comparable to those in control subjects. Patients with VL had decreased IFN-gamma and IL-2 expression, which was restored after cure, and increased IL-10 expression, which persisted after cure. In their response to Leishmania donovani antigen, patients with PKDL showed a 9.6-fold increase in the percentage of IL-10-expressing CD3+CD8+ lymphocytes compared with control subjects, and this percentage decreased with treatment. Patients with PKDL had raised levels of IgG3 and IgG1 (surrogate markers for IL-10), concomitant with increased serum levels of IL-10. CONCLUSIONS: IL-10-producing CD3+CD8+ lymphocytes are important protagonists in the immunopathogenesis of Indian PKDL.     

Kikuchi‐fujimoto disease in fine‐needle aspiration smears: A clinico‐cytologic study of 76 cases of KFD and 684 cases of reactive hyperplasia of the lymph node

Kikuchi‐Fujimoto disease (KFD) is cytologically characterized by a polymorphous lymphoid cell population, abundant karyorrhectic debris and histiocytes, many of which are crescentic (Kikuchi histiocytes). As per reviewed literature, KFD may be confused with tuberculosis, lymphoma, and reactive hyperplasia of lymph nodes (RHLN). Since RHLN was found to be a major challenging factor during routine cytodiagnosis of KFD in our material, we tried to find out the differentiating clinico‐cytologic features between 76 KFD and 684 RHLN cases seen in Kuwait. 63.2% of KFD were in 3rd and 4th decades of life as compared to 40.2% of RHLN (P = 0.0002). Male to female ratio was 1: 2.45 for KFD and 1:1.09 for RHLN (P = 0.0022). Kuwaiti:non‐Kuwaiti ratio was 1:2.04 for KFD and 1.31:1 for RHLN (P < 0.0001). Capillary networks was present in 71.1% of KFD smears and 52.6% of RHLN (P = 0.0023). Tingible body macrophages and dendritic reticulum cells were detected in 17.1% and 22.4%, respectively, in KFD as opposed to 50.1% and 58.8%, respectively, in RHLN (P < 0.0001). Kikuchi histiocyte count ranged from 2 to 36% in KFD and was ≥10% in 31 (40.8%). Rare Kikuchi histiocytes were detected in 16 (2.3%) of RHLN cases but in none of them the count exceeded 1%, whereas their count was >1% in all KFD cases (P < 0.0001). Thus, KFD cases differed significantly from RHLN in respect of age and sex distribution, Kuwaiti:non‐Kuwaiti ratio, and cytomorphologic features such as capillary networks, Kikuchi histiocyte count, dendritic reticulum cells, and tingible body macrophages. Diagn. Cytopathol. 2013;41:288–295. © 2011 Wiley Periodicals, Inc.     

Delivery of therapeutic levels of heparin and low-molecular-weight heparin through a pulmonary route

Although heparin and low-molecular-weight heparins (LMWH) have been widely used clinically as anticoagulants, their broader use has been limited by the lack of noninvasive delivery methods for this class of molecules. In this study, we demonstrate an efficient, rapid, and reproducible delivery system for heparin through the lungs that is not confined to particles of a certain geometric or aerodynamic diameter. Importantly, blood levels after intrapulmonary administration of either heparin or LMWH were comparable to that of s.c. administration but are characterized by a more rapid onset of action (t(1/2) = 40 min vs. 2.5 h, respectively). Furthermore, we show in animal models, that inhaled heparin species efficiently inhibit diseases such as thrombosis and emphysema, and that the repetitive inhalation of formulated LMWH results in no observable toxicity from the delivery of reproducible systemic levels of heparin or LMWH.     

Local and generalized sensitization of thermally evoked defensive behavior in caterpillars

In addition to camouflage and chemical toxicity, many caterpillars defend themselves against predators with sudden sharp movements. For smaller species, these movements propel the body away from the threat, but in larger caterpillars, such as the tobacco hornworm, Manduca sexta, the movement is a defensive strike targeted to a noxious stimulus on the abdomen. Previously, strikes have been studied using mechanical stimulation like poking or pinching the insect, but such stimuli are hard to control. They also introduce mechanical perturbations that interfere with measurements of the behavior. We have now established that strike behavior can be evoked using infra-red lasers to provide a highly localized and repeatable heat stimulus. The latency from the end of an effective stimulus to the start of head movement decreased with repeated stimuli and this effect generalized to other stimulus locations indicating a centrally mediated component of sensitization. The tendency to strike increased with two successive subthreshold stimuli. When delivered to different locations or to a single site, this split-pulse stimulation revealed an additional site-specific sensitization that has not previously been described in Manduca. Previous work shows that strong stimuli increases the effectiveness of sensory stimulation by activating a long-lasting muscarinic cation current in motoneurons. Injection of muscarinic cholinergic antagonists, scopolamine methyl bromide or quinuclidinyl benzilate, only decreased the strike probability evoked by paired stimuli at two locations and not at a single site. This strongly suggests a role of muscarinic acetylcholine receptors in the generalized sensitization of nociceptive responses in caterpillars.