Materials and Methods A 6-year retrospective analysis of 111 patients treated for maxillofacial fractures in Davangere, Karnataka from January 2004 to December 2009 was performed. Variables like age, gender, occupation, type of fracture and mechanism of injury, concomitant injury, mode of treatment, and complications were recorded and assessed.
Results Men between 21 and 30 years were mostly affected (male-to-female ratio = 10:1; age range = 17.60 years; mean 31.7 ± 9.8 [standard deviation]). Most fractures were caused by road traffic accidents (RTAs; 74.7%), followed by interpersonal violence (IPV; 15.8%), falls (4.2%), industrial hazards and animal attacks (2.1% each), and self-inflicted injury (1.1%). Forty-two cases were isolated zygomaticomaxillary complex (ZMC) fractures. The total number of facial fractures documented was 316, of which 222 were purely related to the ZMC; however, 11 were confined only to the midface. Fifty-three cases had concomitant lower jaw fractures, totaling 83. Ophthalmic injuries occurred in 30.52% of cases. Ninety-two cases were treated with open reduction and internal fixation (ORIF), and three cases were managed conservatively. The complication rate observed was 25.26%.
Conclusion RTA continues to be the chief etiological factor in maxillofacial injury with males being affected predominantly. IPV and falls next contribute significantly to the incidence of such injuries. Concomitant injuries, however, require prompt recognition and appropriate management. ORIF still remains the mainstay of treatment; however, fixation devices are constantly being improved upon in an attempt to reduce immobilization time thereby facilitating early return to function with minimal morbidity. Nevertheless, future advances in maxillofacial trauma diagnosis and management are likely to reduce associated morbidity.
maxillofacial trauma; zygomaticomaxillary fractures; mid-face; mandibular fractures; ORIF
Neurocognitive impairments remain prevalent in HIV-1 infected individuals despite current antiretroviral therapies. It is increasingly becoming evident that astrocytes play a critical role in HIV-1 neuropathogenesis through the production of proinflammatory cytokines/chemokines. HIV-1 viral protein R (Vpr) plays an important role in neuronal dysfunction; however, its role in neuroinflammation is not well characterized. The major objective of this study was to determine the effect of Vpr in induction of proinflammatory chemokine CCL5 in astrocytes and to define the underlying mechanism(s).
SVGA astrocytes were either mock transfected or were transfected with a plasmid encoding HIV-1 Vpr, and the cells were harvested at different time intervals. The mRNA level of CCL5 expression was quantified using real-time RT-PCR, and cell culture supernatants were assayed for CCL5 protein concentration. Immunocytochemistry was performed on HIV-1 Vpr transfected astrocytes to check CCL5 expression. Various signaling mechanisms such as p38 MAPK, PI3K/Akt, NF-κB and AP-1 were explored using specific chemical inhibitors and siRNAs.
HIV-1 Vpr transfected astrocytes exhibited time-dependent induction of CCL5 as compared to mock-transfected astrocytes at both the mRNA and protein level. Immunostained images of astrocytes transfected with HIV-1 Vpr also showed much higher accumulation of CCL5 in comparison to untransfected and mock-transfected astrocytes. Pre-treatment with NF-κB (SC514) and PI3K/Akt (LY294002) inhibitor partially abrogated CCL5 mRNA and protein expression levels as opposed to untreated controls after HIV-1 Vpr transfection. Specific siRNAs against p50 and p65 subunits of NF-κB, p38δ MAPK, Akt-2 and Akt-3, and AP-1 transcription factor substantially inhibited the production of CCL5 in HIV-1 Vpr transfected astrocytes.
These results demonstrate the ability of HIV-1 Vpr to induce CCL5 in astrocytes in a time-dependent manner. Furthermore, this effect was observed to be mediated by transcription factors NF-κB and AP-1 and involved the p38-MAPK and PI3K/Akt pathway.
HIV-1; Vpr; CCL5; NF-kB; AP-1; MAPK; PI3K/Akt
The incidence of HIV-associated neurological disorders (HAND) has increased during recent years even though the highly active antiretroviral therapy (HAART) has significantly curtailed the virus replication and increased the life expectancy among HIV-1 infected individuals. These neurological deficits have been attributed to HIV proteins including HIV-1 Tat. HIV-1 Tat is known to up-regulate CCL5 expression in mouse astrocytes, but the mechanism of up-regulation is not known. The present study was undertaken with the objective of determining the mechanism(s) underlying HIV-1 Tat-mediated expression of CCL5 in astrocytes. SVGA astrocytes were transiently transfected with a plasmid encoding Tat, and expression of CCL5 was studied at the mRNA and protein levels using real time RT-PCR and multiplex cytokine bead array, respectively. HIV-1 Tat showed a time-dependent increase in the CCL5 expression with peak mRNA and protein levels, observed at 1 h and 48 h post-transfection, respectively. In order to explore the mechanism(s), pharmacological inhibitors and siRNA against different pathway(s) were used. Pre-treatment with SC514 (NF-κB inhibitor), LY294002 (PI3K inhibitor), AG490 (JAK2 inhibitor) and Janex-1 (JAK3 inhibitor) showed partial reduction of the Tat-mediated induction of CCL5 suggesting involvement of JAK, PI3K/Akt and NF-κB in CCL5 expression. These results were further confirmed by knockdown of the respective genes using siRNA. Furthermore, p38 MAPK was found to be involved since the knockdown of p38δ but not other isoforms showed partial reduction in CCL5 induction. This was further confirmed at transcriptional level that AP-1, C/EBPα and C/EBPγ were involved in CCL5 up-regulation.
This study describes the effect of zinc on monocyte adhesion to endothelial cells under different shear stress regimens, which may trigger atherogenesis. Human umbilical vein endothelial cells were exposed to steady shear stress (15 dynes/cm2 or 1 dyne/cm2) or reversing shear stress (time average 1 dyne/cm2) for 24 hours. In all shear stress regimes, zinc deficiency enhanced THP-1 cell adhesion, while heparinase III reduced monocyte adhesion following reversing shear stress exposure. Unlike other shear stress regimes, reversing shear stress alone enhanced monocyte adhesion, which may be associated with increased H2O2 and superoxide together with relatively low levels of nitric oxide (NO) production. L-NG-Nitroarginine methyl ester (L-NAME) treatment increased monocyte adhesion under 15 dynes/cm2 and under reversing shear stress. After reversing shear stress monocyte adhesion dramatically increased with heparinase III treatment followed by a zinc scavenger. Static culture experiments supported the reduction of monocyte adhesion by zinc following endothelial cell cytokine activation. These results suggest that endothelial cell zinc levels are important for the inhibition of monocyte adhesion to endothelial cells, and may be one of the key factors in the early stages of atherogenesis.
mechanical forces; vascular endothelial cells; heparan sulfate proteoglycans; and reactive oxygen species
HIV-1 envelope protein gp120 has been extensively studied for neurotoxic effects that have been attributed to the increased expression of various proinflammatory cytokines in the CNS. Recently we have shown that methamphetamine (MA) also increases expression of proinflammatory cytokines in astrocytes. However, combined effect of gp120 and MA is not known. The present study was undertaken to determine cumulative effect and the mechanism(s)/pathways involved in the functional interaction between gp120 and MA in SVGA astrocytes. Our results clearly suggest that gp120 and MA affect IL-6 but not IL-8 in a synergistic manner and this synergy was mediated by PI3K/Akt and NF-κB pathways. Inhibition of either of these pathways could abrogate the increased expression of IL-6 due to MA or gp120 alone, as well as the increased expression of IL-6 when the astrocytes were treated with both gp120 and MA. These results were confirmed by both, using chemical inhibitors/siRNA as well as western blotting. This study therefore provides novel information regarding the interaction between MA and gp120 in terms of the expression of IL-6 and the mechanisms underlying potential synergy between MA and gp120 in astrocytes.
Central sulcus hemorrhage is a rare imaging finding that can be related to cerebral amyloidosis in a normotensive non-traumatic elderly patient and present as an isolated finding or in association with other areas of involvement. We report a case presenting with an isolated central sulcus hemorrhage on computed tomography. Further imaging work-up excluded other potential causes of peripheral hemorrhages and established a putative diagnosis of cerebral amyloidosis.
HIV associated neurological disorders (HAND) is a common neurological complication in patients infected with HIV. The proinflammatory cytokines and chemokines produced by astrocytes play a pivotal role in neuroinflammatory processes in the brain and viral envelope gp120 has been implicated in this process. In view of increased levels of CCL5 observed in the CSF of HIV-1 infected patients, we studied the effects of gp120 on CCL5 expression in astrocytes and the possible mechanisms responsible for those effects. Transfection of the SVGA astrocyte cell line with a plasmid encoding gp120 resulted in a time-dependent increase in expression levels of CCL5 in terms of mRNA and protein by 24.6 ± 2.67 fold and 35.2 ± 6.1 fold, respectively. The fluorescent images showed localization of CCL5 in the processes of the astrocytes. The gp120-specific siRNA abrogated the gp120-mediated increase in CCL5 expression. We also explored a possible mechanism for the effects of gp120 on CCL5 expression. Using a specific inhibitor for the NF-κB pathway, we demonstrated that levels of gp120 induction of CCL5 expression can be abrogated by 44.6 ± 4.2 % at the level of mRNA and 51.8 ± 5.0 % at the protein level. This was further confirmed by knocking down NF-κB through the use of siRNA.
AIM: To evaluate the prevalence and severity of pain in patients with chronic stable heart failure (HF) in an outpatient clinic setting.
METHODS: This is a cross-sectional study evaluating symptoms of generalized or specific pain in patients with chronic stable heart failure. A standardized questionnaire (Edmonton Symptom Assessment System) was administered during a routine outpatient clinic visit. The severity of pain and other symptoms were assessed on a 10 point scale with 10 being the worst and 0 representing no symptoms.
RESULTS: Sixty-two patients [age 56 ± 13 years, 51 males, 11 females, mean ejection fraction (EF) 33% ± 17%] completed the assessment. Thirty-two patients (52%) reported any pain of various character and location such as chest, back, abdomen or the extremities, with a mean pain score of 2.5 ± 3.1. Patients with an EF less than 40% (n = 45, 73%) reported higher pain scores than patients with an EF greater than 40% (n = 17, 27%), scores were 3.1 ± 3.3 vs 1.2 ± 1.9, P < 0.001. Most frequent symptoms were tiredness (in 75% of patients), decreased wellbeing (84%), shortness of breath (SOB, 76%), and drowsiness (70%). The most severe symptom was tiredness with a score of 4.0 ± 2.8, followed by decreased wellbeing (3.7 ± 2.7), SOB (3.6 ± 2.8), and drowsiness (2.8 ± 2.8).
CONCLUSION: Pain appears to be prevalent and significantly affects quality of life in HF patients. Adequate pain assessment and management should be an integral part of chronic heart failure management.
Heart failure; Pain; Symptoms; Therapy; Palliative care
The use of methamphetamine (MA) has increased in recent years, and is a major health concern throughout the world. The use of MA has been associated with an increased risk of acquiring HIV-1, along with an increased probability of the acquisition of various sexually transmitted infections. In order to determine the potential effects of MA exposure in the context of an infectious agent, U937 macrophages were exposed to various combinations of MA and bacterial lipopolysaccharide (LPS). Treatment with MA alone caused significant increases in the levels of TNF-α, while treatment with both MA and LPS resulted in significant increases in TNF-α, IL-1β and the chemokine IL-8. The increases in cytokine or chemokine levels seen when cells were treated with both LPS and MA were generally greater than those increases observed when cells were treated with only LPS. Treatment with chemical inhibitors demonstrated that the signal transduction pathways including NF-kB, MAPK, and PI3-Akt were involved in mediating the increased inflammatory response. As discussed in the paper, these pathways appear to be utilized by both MA and LPS, in the induction of these inflammatory mediators. Since these pathways are involved in the induction of inflammation in response to other pathogens, this suggests that MA-exacerbated inflammation may be a common feature of infectious disease in MA abusers.
Methamphetamine (MA) is one of the commonly used illicit drugs and the central nervous system toxicity of MA is well documented. The mechanisms contributing to this toxicity have not been fully elucidated. In this study, we investigated the effect of MA on the expression levels of the proinflammatory cytokines/chemokines, IL-6 and IL-8 in an astrocytic cell line. The IL-6 and IL-8 RNA levels were found to increase by 4.6 ± 0.2 fold and 3.5 ± 0.2 fold, respectively, after exposure to MA for three days. Exposure of astrocytes to MA for 24 hours also caused increased expression of IL-6 and IL-8 at the level of both RNA and protein. The potential involvement of the nuclear factor-Kappa B (NF-κB) pathway was explored as one of the possible mechanism(s) responsible for the increased induction of IL-6 and IL-8 by MA. The MA-mediated increases in IL-6 and IL-8 were significantly abrogated by SC514. We also found that exposure of astrocytes to MA results in activation of NF-κB through the phosphorylation of IκB-α, followed by translocation of active NF-κB from the cytoplasm to the nucleus. In addition, treatment of cells with a specific inhibitor of metabotropic glutamate receptor-5 (mGluR5) revealed that MA-mediated expression levels of IL-6 and IL-8 were abrogated by this treatment by 42.6 ± 5.8% and 65.5 ± 3.5%, respectively. Also, LY294002, an inhibitor of the Akt/PI3K pathway, abrogated the MA-mediated induction of IL-6 and IL-8 by 77.9 ± 6.6% and 81.4 ± 2.6%, respectively. Thus, our study demonstrates the involvement of an NF-κB-mediated signaling mechanism in the induction of IL-6 and IL-8 by MA. Furthermore, we showed that blockade of mGluR5 can protect astrocytes from MA-mediated increases of proinflammatory cytokines/chemokines suggesting mGluR5 as a potential therapeutic target in treating MA-mediated neurotoxicity.
gp120; IL-8; Astrocytes; NF-kB; siRNA
pancreatitis; alcoholic cirrhosis; pseudoaneurysms
Due to very less bioavailability (20%) of Rosuvastatin calcium, an attempt was made to develop and optimize microemulsion formulation. Capmul MCM, Tween 20 and PEG 400 were selected as oil, surfactant and cosurfactant respectively as the drug is having higher solubility in them. 3:1% w/w S:CoS was selected as it gave higher microemulsion area. Optimized batch (ME-1) was selected having 5% Capmul MCM, 50% Tween 20:PEG 400 and 45% water based on evaluation parameters globule size, zeta potential, PDI, % transmittance.
Microemulsion; bioavailability; solubility enhancement
Acute dacryoadenitis is an uncommon condition that involves inflammation of the lacrimal gland. In rare instances, dacryoadenitis may be bilateral. A delay in proper treatment of an otherwise simple case of dacryoadenitis may lead to significant soft tissue morbidity such as cellulitis, lacrimal gland abscess, or orbital abscess. We report the case of a 24-year-old male who presented to the emergency department with acute bilateral dacryoadenitis. The patient's symptoms did not respond to oral antibiotics and he subsequently required admission for intravenous antibiotics. During his hospitalization the patient had diagnostic testing to try to determine the etiology for his symptoms. The unique aspects of managing a case of bilateral dacryoadenitis as well as treatment recommendations are discussed in this case report.
Dacryoadenitis; eye diseases; lacrimal apparatus diseases
In addition to its role in virus entry, HIV-1 gp120 has also been implicated in HIV-associated neurocognitive disorders. However, the mechanism(s) responsible for gp120-mediated neuroinflammation remain undefined. In view of increased levels of IL-6 in HIV-positive individuals with neurological manifestations, we sought to address whether gp120 is involved in IL-6 over-expression in astrocytes. Transfection of a human astrocyte cell line with a plasmid encoding gp120 resulted in increased expression of IL-6 at the levels of mRNA and protein by 51.3±2.1 and 11.6±2.2 fold respectively; this effect of gp120 on IL-6 expression was also demonstrated using primary human fetal astrocytes. A similar effect on IL-6 expression was observed when primary astrocytes were treated with gp120 protein derived from different strains of X4 and R5 tropic HIV-1. The induction of IL-6 could be abrogated by use of gp120-specific siRNA. Furthermore, this study showed that the NF-κB pathway is involved in gp120-mediated IL-6 over-expression, as IKK-2 and IKKβ inhibitors inhibited IL-6 expression by 56.5% and 60.8%, respectively. These results were also confirmed through the use of NF-κB specific siRNA. We also showed that gp120 could increase the phosphorylation of IκBα. Furthermore, gp120 transfection in the SVGA cells increased translocation of NF-κB from cytoplasm to nucleus. These results demonstrate that HIV-1 gp120-mediated over-expression of IL-6 in astrocytes is one mechanism responsible for neuroinflammation in HIV-infected individuals and this is mediated by the NF-κB pathway.
Insulin resistance in skeletal muscle is a key phenotype associated with type 2 diabetes (T2D) for which the molecular mediators remain unclear. We therefore conducted an expression analysis of human muscle biopsies from patients with T2D; normoglycemic but insulin-resistant subjects with a parental family history (FH+) of T2D; and family history-negative control individuals (FH–). Actin cytoskeleton genes regulated by serum response factor (SRF) and its coactivator megakaryoblastic leukemia 1 (MKL1) had increased expression in T2D and FH+ groups. Furthermore, striated muscle activator of Rho signaling (STARS), an activator of SRF, was upregulated in T2D and FH+ and was inversely correlated with insulin sensitivity. Skeletal muscle from insulin-resistant mice recapitulated this gene expression pattern and showed reduced G-actin and increased nuclear localization of MKL1, each of which regulates SRF activity. Overexpression of MKL1 or reduction in G-actin decreased insulin-stimulated Akt phosphorylation, whereas reduction of STARS expression increased insulin signaling and glucose uptake. Pharmacological SRF inhibition by CCG-1423 reduced nuclear MKL1 and improved glucose uptake and tolerance in insulin-resistant mice in vivo. Thus, SRF pathway alterations are linked to insulin resistance, may contribute to T2D pathogenesis, and could represent therapeutic targets.
The exact mechanism underlying HIV-associated neurocognitive disorders still remains largely unresolved. However, viral genes (for example gp120 and tat) and their effect on cytokine/chemokine expressions have been linked with neuroinflammation. Conversely, interlekin-8 (IL-8) is a known proinflammatory chemokine and is known to be over-expressed in human brain microvascular endothelial cells in response to gp120. In this study, we sought to address whether HIV-1gp120 could affect IL-8 expression in astrocytes and whether the NF-κB pathway is involved in this phenomenon.
SVGA astrocytes were transfected with a plasmid expressing HIV-1 pSyn gp120 JR-FL using Lipofectamine2000. The cells were harvested at different time points after transfection, and total cellular RNA was used for quantification of IL-8 using a real time PCR. IL-8 protein expression was also determined in supernatants collected at different time points after transfection. Involvement of the NF-κB pathway was addressed using both pharmacological inhibitors and an siRNA approach. In order to explore gene specificity, gp120-specific siRNAs were designed and IL-8 expression was monitored at both mRNA and protein levels.
Gp120 increased IL-8 expression both at mRNA and protein levels by 7.1 ± 1.04 and 2.41 ± 0.35 fold at 6 and 48 hours post-transfection, respectively. This increase was time-dependent and was abrogated by use of gp120-specific siRNA. We have also shown that the NF-κB pathway is involved in gp120-mediated IL-8 overexpression as IKK-2 and IKKβ inhibitors inhibited IL-8 expression by 63.5% and 57.5%, respectively at the mRNA level, and by 67.3% and 58.6% at the protein level. These results were also confirmed with use of NF-κB-specific siRNA.
These results indicate that gp120 can modulate expression of a pro-inflammatory chemokine (IL-8) in astrocytes in a time-dependent manner with significant up-regulation at different times. This phenomenon is specific and is mediated by the NF-κB pathway.
Tennis leg is caused by a rupture of the medial head of the gastrocnemius muscle, usually at its distal musculotendinous junction region. However, tears in this muscle and its tendon are also included under the term ‘tennis leg’. It is seen regularly in practice and is an important cause of a painful calf. The common USG findings include: disruption of the pinnate pattern of the distal medial gastrocnemius, usually near the junction of the triceps surae (which is the echogenic line between the gastrocnemius, the soleus, and the plantaris muscles), fluid tracking along the fascia, adjacent hematoma, and intramuscular tears as well as hematomas. USG is useful for confirming the diagnosis, excluding other causes of a painful calf, for assessing the severity of the disease, and in follow-up.
Avulsion; gastrocnemius ; magnetic resonance imaging (MRI); sonography; tear; Tennis leg