The chemistry and pharmacology of alkaloids and allied nitrogen compounds from Artemisia species: A review

Several reviews have been published on Artemisia's derived natural products, but it is the first attempt to review the chemistry and pharmacology of more than 80 alkaloids and allied nitrogen compounds obtained from various Artemisia species (covering the literature up to June 2018). The pharmacological potential and unique skeleton types of certain Artemisia's alkaloids provoke the importance of analyzing Artemisia species for bioactive alkaloids and allied nitrogen compounds. Among the various types of bioactive Artemisia's alkaloids, the main classes were the derivatives of rupestine (pyridine–sesquiterpene), lycoctonine (diterpene), pyrrolizidine, purines, polyamine, peptides, indole, piperidine, pyrrolidine, alkamides, and flavoalkaloids. The rupestine derivatives are Artemisia's characteristic alkaloids, whereas the rest are common alkaloids found in the family Asteraceae and chemotaxonomically links the genus Artemisia with the tribes Anthemideae. The most important biological activities of Artemisia's alkaloids are including hepatoprotective, local anesthetic, β‐galactosidase, and antiparasitic activities; treatment of angina pectoris, opening blocked arteries, as a sleep‐inducing agents and inhibition of HIV viral protease, CYP450, melanin biosynthesis, human carbonic anhydrase, [3H]‐AEA metabolism, kinases, and DNA polymerase β¹. Some of the important nitrogen metabolites of Artemisia include pellitorine, zeatin, tryptophan, rupestine, and aconitine analogs, which need to be optimized and commercialized further.     

Nanoparticle encapsulated antitubercular drugs as a potential oral drug delivery system against murine tuberculosis

Patient non-compliance is the major drawback associated with the long-duration chemotherapy of tuberculosis (TB); hence, reduction in dosing frequency forms an important therapeutic strategy. The present study reports the formulation of three frontline antitubercular drugs (ATD), i.e. rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) encapsulated in poly (DL-lactide-co-glycolide) (PLG) nanoparticles. Drug encapsulation efficiencies were 56.9+/-2.7% for RIF, 66.3+/-5.8% for INH and 68+/-5.6% for PZA. Following a single oral administration of these preparations to mice, the drugs could be detected in the circulation for 6 days (RIF) and 9 days (INH/PZA), whereas therapeutic concentrations in the tissues were maintained for 9-11 days. Further, on oral administration of drug-loaded nanoparticles to Mycobacterium tuberculosis-infected mice at every 10th day, no tubercle bacilli could be detected in the tissues after 5 oral doses of treatment. Therefore, nanoparticle-based ATD therapy forms a sound basis for reduction in dosing frequency for better management of TB.     

Acute subarachnoid hemorrhage: An unusual clinical presentation of cerebral venous sinus thrombosis

Ruptured cerebral aneurysm is the most common cause of spontaneous subarachnoid hemorrhage (SAH). Rarely cerebral venous sinus thrombosis (CVST) may present initially as acute SAH, and clinically mimics aneurysmal bleed. We report 2 cases of CVST who presented with severe headache associated with neck pain and focal seizures. Non-contrast brain CT showed SAH, involving the sulci of the convexity of hemisphere (cSAH) without involving the basal cisterns. Both patients received treatment with anticoagulants and improved. Awareness of this unusual presentation of CVST is important for early diagnosis and treatment. The purpose of this paper is to emphasize the inclusion of vascular neuroimaging like MRI with venography or CT venography in the diagnostic workup of SAH, especially in a patient with strong clinical suspicion of CVST or in a patient where neuroimaging showed cSAH.Spontaneous subarachnoid hemorrhage (SAH) suggests the presence of a vascular lesion, most commonly ruptured cerebral aneurysm. It is rare for SAH to be associated with cerebral venous sinus thrombosis (CVST), and its location is usually different from the arterial aneurysms.1,2 The exact pathogenesis of SAH associated with CVST remains unknown; however, it is believed that it is probably induced by the rupture of dilated thin-walled cortical veins.1 Diagnosis of CVST associated with SAH usually depends on a high index of clinical suspicion combined with radiologic confirmation, so that appropriate treatment can be timely initiated. To date, 74 cases of CVST with radiological evidence of SAH, usually seen at the cerebral convexities, have been reported in the literature.3,4We are reporting 2 cases of superior sagittal sinus (SSS) thrombosis that presented initially with SAH. Our objective in presenting these cases is to highlight the fact that CVST may present early as SAH, and vascular neuroimaging should be considered in selected cases, especially those cases, in which cerebral aneurysm is not detected and there is still a clinical suspicious of CVST. We also have addressed the non-aneurysmal convexity SAH (cSAH) which is being increasingly recognized with characteristic radiological pattern of venous SAH, as opposed to aneurysmal SAH. The use of systemic anticoagulation as an initial therapy of CVST, even in the presence of SAH is also briefly discussed.     

Serology based disease status of Pakistani population infected with Hepatitis B virus

Background  

The infection rate of hepatitis B virus is continuously increasing in Pakistan. Therefore, a comprehensive study of epidemiological data is the need of time.     

Small interfering RNAs based therapies for intracerebral hemorrhage: challenges and progress in drug delivery systems

Intracerebral hemorrhage(ICH)is a subtype of stroke associated with higher rates of mortality.Currently,no effective drug treatment is available for ICH.The molecular pathways following ICH are complicated and diverse.Nucleic acid therapeutics such as gene knockdown by small interfering RNAs(siRNAs)have been developed in recent years to modulate ICH’s destructive pathways and mitigate its outcomes.However,siRNAs delivery to the central nervous system is challenging and faces many roadblocks.Existing barriers to systemic delivery of siRNA limit the use of naked siRNA;therefore,siRNA-vectors developed to protect and deliver these therapies into the specific-target areas of the brain,or cell types seem quite promising.Efficient delivery of siRNA via nanoparticles emerged as a viable and effective alternative therapeutic tool for central nervous system-related diseases.This review discusses the obstacles to siRNA delivery,including the advantages and disadvantages of viral and nonviral vectors.Additionally,we provide a comprehensive overview of recent progress in nanotherapeutics areas,primarily focusing on the delivery system of siRNA for ICH treatment.