Antimicrobial and antileishmanial activities of hypocrellins A and B

Hypocrellins A and B were evaluated for in vitro antimicrobial and antileishmanial activities. Hypocrellin A exhibited promising activity against Candida albicans and moderate activity against Staphylococcus aureus, methicillin-resistant S. aureus, Pseudomonas aeruginosa, and Mycobacterium intracellulare. Hypocrellin B showed weak antimicrobial activities. Hypocrellin A exhibited potent antileishmanial activity, while hypocrellin B was only moderately active. These results of promising antifungal and antileishmanial activity of hypocrellin A may be useful for further structure-activity relationship and in vivo studies.     

Clinico-radiological spectrum of reversible splenial lesions in children

Recently, many cases of children presenting reversible splenial lesions during febrile illness (RESLEF) have been reported; however, their overall clinico-radiological features are unclear.     

Clinical and functional outcomes in Middle Eastern patients with idiopathic pulmonary fibrosis

Background: Baseline clinical and physiological variables have been described as relevant predictors of survival among patients with idiopathic pulmonary fibrosis (IPF). However, substantial heterogeneity in both survival time and mortality has been observed with many of these predictive factors. The incidence and mortality rates of IPF vary from country to country, with race potentially contributing to such variations. Objective: We sought to describe baseline clinical features to determine their predictive value among Middle Eastern patients diagnosed with IPF. Methods: We retrospectively examined 61 patients diagnosed with IPF at a university hospital in Riyadh, Saudi Arabia. Results: At presentation, most patients exhibited either dyspnea or cough. The median survival time for all patients was 92 months. Diminished survival was significantly associated with finger clubbing (P = 0.01). Factors not influencing survival were age, gender, percent predicted forced vital capacity, percent predicted forced expiratory volume in 1 s, percent predicted total lung capacity, percent predicted diffusion capacity of the lung for carbon monoxide and resting oxygen saturation. Conclusions: Finger clubbing is a significant predictive variable and was associated with a 5‐fold increase in mortality. Other baseline demographic characteristics as well as pulmonary function tests were not predictive of prognosis in Middle Eastern patients with IPF. It appears that IPF patients of Middle Eastern descent have a longer median survival curve compared to other races. Please cite this paper as: Alhamad EH, Masood M, Shaik SA and Arafah M. Clinical and functional outcomes in Middle Eastern patients with idiopathic pulmonary fibrosis. The Clinical Respiratory Journal 2008; 2: 220–226.     

Synthesis of tetrahydrochromenes and dihydronaphthofurans via a cascade process of [3 + 3] and [3 + 2] annulation reactions: mechanistic insight for 6-endo-trig and 5-exo-trig cyclisation

Substituted tetrahydrochromenes and dihydronaphthofurans are easily accessible by the treatment of β-tetralone with trans-β-nitro styrene derived Morita–Baylis–Hillman (MBH) acetates through a formal [3 + 3]/[3 + 2] annulation. The reaction proceeds through a cascade Michael/oxa-Michael pathway with moderate to good yields. A DFT study was carried out to account for the formation of the corresponding six and five-membered heterocycles via 6-endo-trig and 5-exo-trig cyclization.

A [3 + 3] and [3 + 2] annulation strategy using nitrostyrene derived MBH primary and secondary nitro allylic acetate for the construction of tetrahydrochromenes and dihydronaphthofurans at room temperature.

The ability to synthesize diverse molecules utilizing nitro allylic MBH acetates in various cascade reactions has received considerable interest.¹ A few molecules synthesized using nitro allylic acetates have shown promising cytotoxic, trypanocidal and AchE inhibition² activity in pharmaceutical and medicinal chemistry. Nitro allylic MBH acetates have been used as main precursors in organocatalysis³ and heterocyclic chemistry,⁴ and as bicyclic skeletons⁵ for the construction of elegant building blocks like tetrahydro-pyranoquinolinones,⁶ sulfonyl furans,⁷ pyranonaphthoquinones,⁸ arenopyrans/arenylsulfanes,⁹ triazoles,^10a tetrasubstituted furans,^10b fused furans,^10c,d tetrasubstituted pyrroles,^11a benzofuranones,^11b and tetrahydropyrano scaffolds/pyranocoumarins.¹² The nitro allylic MBH-acetates can also undergo asymmetric benzylic^13a and allylic alkylation^13b reactions as well as kinetic resolution [KR]^13c,d under normal conditions. These acetates undergo a range of cascade [2 + 3],¹⁴ [3 + 2]¹⁵ and [3 + 3]¹⁶ ring annulation reactions using different substrates. They have been widely utilized in [3 + 2]^17a and [3 + 3]^17b annulation reactions due to their unique nature of 1,2-/1,3-biselectrophilic reactivity to form either five or six membered rings depending on the nature of nucleophiles employed in the reaction^17c,d These adducts are also stable under NHC catalytic conditions to yield cyclopentanes.¹⁸Peng-Fei Xu et al. (Scheme 1, eqn (a)) synthesised tetrahydropyranoindoles through organocatalytic asymmetric C–H functionalization of indoles via [3 + 3] annulation through 6-endo trig cyclization.¹⁹ The Namboothiri group recently developed a metal free regioselective synthesis of α-carbolines via [3 + 3] annulation involving secondary MBH acetate (Scheme 1, eqn (b)).²⁰ Previously, our group carried out a [3 + 3] cyclization reaction of β-naphthol with primary MBH acetate to study the scope of S_N2′ vs. S_N2 reaction.²¹ With our ongoing interest in using nitro styrene derived MBH adducts²² explored the reactivity of primary and secondary MBH acetate with β-tetralone 1 as our model reaction. Initially, the reaction carried out using β-tetralone 1 with primary MBH-acetate 2, predominantly gave a tetrahydrochromene 3via [3 + 3] annulation involving 6-endo trig cyclization through Michael/oxa-Michael cascade process. The possible dihydronaphthofuran product was not observed under the present conditions as primary MBH acetate 2 acts as 1,3-biselectrophile instead of 1,2-biselectrophile (Scheme 1, eqn (c)).Open in a separate windowScheme 1[3 + 3] and [3 + 2] annulation reactions using 1°- and 2°-nitro allylic MBH acetate.On the other hand, the reaction of β-tetralone 1 with secondary MBH acetate 4 gave dihydronaphthofuran instead of the possible tetrahydrochromene product due to the 1,2-biselectrophile nature of secondary MBH acetate (Scheme 1, eqn (d)). The formation of dihydronaphthofuran 5 occurs in an S_N2′ fashion via [3 + 2] annulation involving 5-exo-trig cyclization through Michael followed by intramolecular oxa-Michael reaction with the elimination of HNO₂. Subsequently, we have carried out a DFT calculation to prove the formation of tetrahydrochromene 3 using primary MBH acetate 2 and dihydronaphthofuran 5 in the case of secondary MBH acetate 4.Initially, we carried out the optimization conditions for constructing tetrahydrochromenes 3a using β-tetralone 1 with MBH nitro allylic primary acetate 2a with different bases and solvents. Reaction with organic base, i.e. DABCO using a polar aprotic solvent such as acetonitrile at room temperature gave the desired product in 27% (23 (CCDC-2149875) (

The zinc finger protein ZPR1 is a potential modifier of spinal muscular atrophy

Spinal muscular atrophy (SMA) is caused by mutation of the Survival Motor Neurons 1 (SMN1) gene and is characterized by degeneration of spinal motor neurons. The severity of SMA is primarily influenced by the copy number of the SMN2 gene. Additional modifier genes that lie outside the SMA locus exist and one gene that could modify SMA is the Zinc Finger Protein (ZPR1) gene. To test the significance of ZPR1 downregulation in SMA, we examined the effect of reduced ZPR1 expression in mice with mild and severe SMA. We report that the reduced ZPR1 expression causes increase in the loss of motor neurons, hypermyelination in phrenic nerves, increase in respiratory distress and disease severity and reduces the lifespan of SMA mice. The deficiency of SMN-containing sub-nuclear bodies correlates with the severity of SMA. ZPR1 is required for the accumulation of SMN in sub-nuclear bodies. Further, we report that ZPR1 overexpression increases levels of SMN and promotes accumulation of SMN in sub-nuclear bodies in SMA patient fibroblasts. ZPR1 stimulates neurite growth and rescues axonal growth defects in SMN-deficient spinal cord neurons from SMA mice. These data suggest that the severity of disease correlates negatively with ZPR1 levels and ZPR1 may be a protective modifier of SMA.     

Pre-operative Assessment of Anatomical Position of Inferior Alveolar Nerve and Its Significance in Bilateral Sagittal Split Osteotomy

The aim of this study is to investigate the position and course of the mandibular canal through the ramus, angle and body of mandible using computed tomographic (CT) imaging pre-operatively and to relate these predetermined values intra-operatively to perform sagittal split ramus osteotomies. Pre-operative CT scans were taken and four points were marked at mandibular foramen, mandibular angle, mandibular body and midpoint and different dimensions of IAN were measured to localize the inferior alveolar nerve. With the obtained values, precise osteotomy cuts were made intra-operatively and intra-operative measurements for position of IAN were noted. Based on the preoperative CT measurements, the chance to encounter IAN bundle, during surgery was evaluated. The present study proved that pre-operative CT imaging prior to BSSO surgical procedure is an effective way to investigate the position and course of the IAN canal through the framework of the mandible and by interpolating these dimensions intra operatively, reduces the risk of direct injury to the IAN bundle.     

Length of MRI signal may predict outcome in advanced cervical spondylotic myelopathy

Objective:

To study clinical and radiological factors that may correlate with independent walking (IW) following advanced cervical spondylotic myelopathy (CSM) surgery.

Methods:

A retrospective case series including all advanced CSM patients (Nurick 4 and 5) who underwent surgery from 2003-2010 in the Division of Neurosurgery, Department of Surgery, College of Medicine, King Saud University and King Khalid University Hospital, Riyadh, Saudi Arabia. Only patients with 6 months or more follow-up were included. A neuroradiologist who was blinded to the clinical data reviewed all MRI studies.

Results:

Forty-three patients were included (83% males, mean follow-up 29 months). A better preoperative neurological status was a positive predictor of IW after surgery (85.7% Nurick 4 versus 36.4% Nurick 5, p=0.001). Independent walking was less likely in patients with the following MRI features: longer T2-weighted image (T2WI) signal changes (p=0.001), well-circumscribed T2WI signal changes (p=0.028), T1WI hypointensity (p=0.001), and narrow spinal canal diameter (p=0.048). Multivariate regression revealed that both an increased T2WI signal change length and T1WI hypointensity were independent predictors. The risk of dependent walking increased by 1.35 times as the T2WI signal intensity length increased by one mm, and by 14-times with T1WI hypointensity.

Conclusions:

Regaining IW after surgery in patients with advanced CSM was less likely for cases showing MRI features of longer T2WI signal changes and T1WI hypointensity. Better baseline walking, less defined T2WI signal change, and a wider spinal canal were good prognostic factors.Cervical spondylotic myelopathy (CSM) may lead to significant disability.1-3 Progressive compression of the spinal cord causes chronic ischemia, local inflammatory response, and endothelial cell loss that may result in permanent spinal cord damage.4 In addition, there is an enhanced permeability in the blood-spinal cord barrier, leading to contact between the peripheral immune system and the spinal cord. Subsequently, there is an increased inflammatory reaction, resulting in more adverse effects on the spinal cord.5 Eventually, the spinal cord develops cystic cavitation, gliosis, degeneration of the central grey and medial white matter, Wallerian degeneration of the posterior columns and posterolateral tracts, and a loss of anterior horn cells. These changes are reflected on the clinical presentation and MRI features of the patients. The ability to detect changes related to spinal cord compression plays an important role in predicting clinical and functional outcomes. Several clinical and radiological factors have been studied as potential predictors for functional outcome. Relevant clinical predictors include the patient’s age at diagnosis, the duration of symptoms prior to surgery, medical comorbidities, the preoperative neurological status, and the surgical procedure performed.6,7The MRI predictors of unfavorable outcome include hypointensity on T1-weighted images (T1WI), the type of signal intensity on T2-weighted images (T2WI), and a reduction of the spinal canal diameter.6,8-12 The correlation between the length of signal change on T2WI MRI sequences and clinical outcome after surgery has not been established. Changes in the internal structure of the spinal cord could appear as alterations in the signal intensity on T1- and T2-weighted MRI sequences.8,13 Hyperintensity on T2WI corresponds to focal gliosis, myelomalacia, vascular ischemia, and edema. Therefore, it is possible that patients with longer MRI signals experience less favorable clinical recoveries after surgery, particularly if the changes correspond to hypointensity on T1WI. In the current study, our objective was to assess the correlation between clinical and MRI features and independent walking (IW) after surgery in an attempt to predict functional recovery. Only patients with advanced myelopathy were included to avoid any bias that may result from involvement of patients with different disease severity.