Biosimilars in rheumatology: recommendations for regulation and use in Middle Eastern countries

The increasing availability of biosimilar medicines in Middle Eastern regions may provide an opportunity to increase the number of rheumatology patients who have access to traditionally more expensive biologic medicines. However, as well as a lack of real-world data on the use of biosimilar medicines in practice, the availability of intended copies in the region may undermine physician confidence in prescribing legitimate biosimilar medicines. There is a need for regional recommendations for healthcare professionals to ensure that biosimilar drugs can be used safely. Therefore, a literature search was performed with the aim of providing important recommendations for the regulation and use of biosimilar medicines in the Middle East from key opinion leaders in rheumatology from the region. These recommendations focus on improving the availability of relevant real-world data, ensuring that physicians are aware of the difference between intended copies and true biosimilars and ensuring that physicians are responsible for making any prescribing and switching decisions.     

Retained periorbital and intracranial air-gun pellets causing sclopetaria and visual loss

Three healthy males presented on separate occasions to the emergency room at the King Khaled Eye Specialist Hospital (KKESH) after sustaining trauma by air-gun pellets. Clinical examination indicated sclopetaria in all the cases. The foreign bodies (air-gun pellets) were imbedded in different locations (subconjunctival, intraorbital, and intracranial). All cases resulted in a profound and permanent visual loss. The management of this traumatic injury is discussed and concurs with the published literature.     

Anabolic androgenic steroid induced necrotising myopathy

We describe the case of a 23-year-old gentleman who developed a severe generalised necrotising myopathy. Initially presenting with features of a virus-induced polymyositis, both symptomatic and biochemical improvements were initially achieved with glucocorticoid-based immunosuppression. Subsequently he represented with evidence of severe generalised rhabdomyolysis (creatinine kinase peaking at 210,000 U/L). Rendered anuric from the myogloburic assault, he required intensive care support from the development of multi-organ failure. Subsequent investigations failed to demonstrate an infective, inflammatory, metabolic or inherited aetiology. Muscle biopsy demonstrated severe generalised necrotising myopathy in the notable absence of inflammation. Confidential discussion with the patient and relatives confirmed a suspicion of anabolic androgenic steroid (AAS) abuse. There is limited literature as to the toxic effect of AAS compounds on muscle tissue, and these tend to focus on localised disease. Indeed, AAS have consistently been shown in animal models to produce a generalised myotrophic state. Apart from the social uses of such compounds, the scope for their supervised use in various medical conditions has been established since the 1960s.     

Gestational variations in the biochemical composition of the fetal fluids and maternal blood serum in goat

The purpose of this study was to determine the values of some metabolites, ions, and enzymes in maternal blood serum and fetal fluids in relation to pregnancy stage in singleton pregnant goats. Gravid uteri of goats were collected from local abattoirs. The allantoic and amniotic fluids as well as maternal blood samples were collected. Fetal age was determined according to crown–rump length by applying the age estimation formula that previously was presented for goat. The pregnancies were divided into five stages as: stage I (0–30?days), stage II (31–60?days), stage III (61–90?days), stage IV (91–120?days), and stage V (121?days to term). With the progress of pregnancy, the biochemical levels of fetal fluids and maternal serum changed as follows: there was a rise of total protein, urea, and creatinine concentrations in fetal fluids and serum; the level of glucose in serum, potassium, and ALK in fetal fluids and calcium and phosphorus in allantoic fluid increased; triglyceride and sodium contents of fetal fluids and serum decreased; glucose in fetal fluids, AST and LDH in serum and allantoic fluid, potassium and ALT in serum, and calcium and phosphorus in amniotic fluid and serum dropped; the values of AST, ALT, and ALK in amniotic fluid remained unchanged; and the levels of cholesterol and LDH in amniotic and allantoic fluids were constant in the whole gestation periods. The serum cholesterol value showed a significant decrease from stages 1 to 2 of pregnancy. But, it was not significant from stages 2 to 5 of gestation.     

Yohimbine Depresses Excitatory Transmission in BNST and Impairs Extinction of Cocaine Place Preference Through Orexin-Dependent,Norepinephrine-Independent Processes

The alpha2 adrenergic receptor (α₂-AR) antagonist yohimbine is a widely used tool for the study of anxiogenesis and stress-induced drug-seeking behavior. We previously demonstrated that yohimbine paradoxically depresses excitatory transmission in the bed nucleus of the stria terminalis (BNST), a region critical to the integration of stress and reward pathways, and produces an impairment of extinction of cocaine-conditioned place preference (cocaine-CPP) independent of α₂-AR signaling. Recent studies show yohimbine-induced drug-seeking behavior is attenuated by orexin receptor 1 (OX₁R) antagonists. Moreover, yohimbine-induced cocaine-seeking behavior is BNST-dependent. Here, we investigated yohimbine-orexin interactions. Our results demonstrate yohimbine-induced depression of excitatory transmission in the BNST is unaffected by alpha1-AR and corticotropin-releasing factor receptor-1 (CRFR₁) antagonists, but is (1) blocked by OxR antagonists and (2) absent in brain slices from orexin knockout mice. Although the actions of yohimbine were not mimicked by the norepinephrine transporter blocker reboxetine, they were by exogenously applied orexin A. We find that, as with yohimbine, orexin A depression of excitatory transmission in BNST is OX₁R–dependent. Finally, we find these ex vivo effects are paralleled in vivo, as yohimbine-induced impairment of cocaine-CPP extinction is blocked by a systemically administered OX₁R antagonist. These data highlight a new mechanism for orexin on excitatory anxiety circuits and demonstrate that some of the actions of yohimbine may be directly dependent upon orexin signaling and independent of norepinephrine and CRF in the BNST.