Pulmonary manifestations in Egyptian patients with systemic sclerosis

Aim of the work

To study the occurrence of interstitial lung disease (ILD) and pulmonary hypertension (PH) in a cohort of Egyptian systemic sclerosis (SSc) patients and their relation to clinical variables.

Long-term outcomes in patients initially responsive to selective laser trabeculoplasty

AIM:To determine the long-term effects of selective laser trabeculoplasty (SLT) on intraocular pressure (IOP) and the number of medications used up to 5y following treatment in glaucoma patients receiving maximally tolerated medical therapy (MTMT).METHODS:The Wills Eye Hospital Glaucoma Research Center retrospectively reviewed the charts of glaucoma patients who underwent SLT after receiving MTMT. Eyes that did not achieve their target pressure within 3mo following SLT were excluded from the study. Changes in mean IOP and number of glaucoma medications used were analyzed at 1, 3, and 5y following SLT.RESULTS:Seventy-five eyes of 67 patients were included in the study. Fifteen eyes that received SLT failed to achieve their target pressure within 3mo and were excluded from the study. The average follow-up time was 37.4mo (±14.4). Mean IOP was significantly reduced 1y after treatment (P=0.005). It was also reduced 3, 5y after treatment without reaching statistical significance (P=0.20 and P=0.072, respectively). There was a significant decrease in mean number of medications used 1, 3, 5y after treatment (P<0.001, P<0.001, and P=0.039, respectively). In the span of 5y, 2 eyes (2.7%) underwent repeat SLT, 7 eyes (9.3%) underwent glaucoma surgery and an additional 3 eyes (4.0%) underwent both.CONCLUSION:SLT significantly reduced the number of glaucoma medications used 5y following treatment in glaucoma patients receiving MTMT. SLT may delay operating-room surgery.     

Neuromuscular Ultrasound of Cranial Nerves

Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed.     

Patients’ perceived purpose of clinical informed consent: Mill’s individual autonomy model is preferred

Background

Although informed consent is an integral part of clinical practice, its current doctrine remains mostly a matter of law and mainstream ethics rather than empirical research. There are scarce empirical data on patients’ perceived purpose of informed consent, which may include administrative routine/courtesy gesture, simple honest permission, informed permission, patient-clinician shared decision-making, and enabling patient’s self decision-making. Different purposes require different processes.

Methods

We surveyed 488 adults who were planning to undergo or had recently undergone written informed consent-requiring procedures. Perceptions of informed consent purpose (from norm and current practice perspectives) were explored by asking respondents to rank (1?=?most reflective) 10 randomly-presented statements: “meaningless routine”, “courtesy gesture” “litigation protection”, “take away compensation rights”, “inform patient’, “make sure patient understand”, “document patient’s decision”, “discover patient’s preferences”, “have shared decision”, and “help patient decide”.

Results

Respondents’ mean (SD) age was 38.3 (12.5); 50.4% were males, 56.8% had?≥?college education, and 37.3% had undergone a procedure. From the norm perspective, the least reflective statement was “meaningless routine” (ranked 1–3 by 2.6% of respondents) and the most reflective statements were “help patient decide”, “make sure patient understand”, and “inform patient” (ranked 1–3 by 65%, 60%, and 48% of respondents with median [25%,75%] ranking scores of 2 [1,5], 3 [2,4], and 4 [2,5], respectively). Compared to their counterparts, males and pre-procedure respondents ranked “help patient decide” better, whereas females and post-procedure respondents ranked “inform patient” better (p?=?0.007 to p?<?0.001). Age was associated with better ranking of “help patient decide” and “make sure patient understand” statements (p?<?0.001 and p?=?0.002, respectively), which were ranked 1–3 by only 46% and 42% of respondents from the current practice perspective (median ranking score 4 [2,6], p?<?0.001 vs. norm perspective for both).

Conclusions

1) the informed consent process is important to patients, however, patients vary in their views of its purpose with the dominant view being enabling patients’ self decision-making, 2) males, pre-procedure, and older patients more favor a self decision-making purpose, whereas females and post-procedure patients more favor an information disclosure purpose, and 3) more self decision-making and more effective information disclosure than is currently practiced are desired. An informed consent process consistent with Mill’s individual autonomy model may be suitable for most patients.     

Effect of a single intrastriatal rotenone injection on oxidative stress and neurodegeneration in the rat brain

We investigated the effect of a single injection of rotenone into the striatum on the development of oxidative stress, nigrostriatal cell injury and motor alterations in rats. Rotenone (1, 3, 5 and 9 mM; 5 μL/rat) or the vehicle (dimethyl sulfoxide) was injected into the right striatum. Control rats received the vehicle only. Rats were allowed to recover from the operation and were tested for behavioural changes on 7th and 30th days after rotenone injection. Biochemical markers of oxidative stress including malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, paraoxonase 1 (PON1) activity and Q10 enzyme as well as monoamine neurotransmitters in the brain were determined after 30 days of rotenone treatment. Histopathology and tyrosine hydroxylase immunohistochemistry were also performed. Results: Intrastriatal injection of rotenone at 9 mM caused immediate death of rats. No mortality was observed with the lower concentrations of the pesticide. Rotenone at 1–5 mM resulted in increased brain oxidative stress in a dose-dependent manner. MDA increased by 23.5–64.9 %, while GSH decreased by 20.4–24.1 % in the contralateral cerebral hemisphere. Nitric oxide increased by 20.2–41.7 % in ipsilateral cortex. PON1 activity decreased by 12.5–38.2 % in ipsilateral cerebral cortex and by 31.2–65.3 % in ipsilateral striatum, respectively, but coenzyme Q10 increased in the ipsilateral cortex by 21–26.3 %. There was decreased dopamine and serotonin in the ipsilateral striatum after rotenone injection. Tyrosine hydroxylase immunoreactivity was markedly decreased in ipsilateral substantia nigra in the rotenone-treated in contrast to the vehicle-treated rats. Rotenone increased the number of degenerated cells in substantia nigra in a dose-dependent manner. It also caused depletion of pigment granules from cells. Degenerative changes were also observed in the contralateral hippocampus and cortex especially after the highest dose of rotenone. The number of spontaneous rears made during 30 min in the cylinder was decreased in both limbs; the decrease being more evident in the ipsilateral side. Thus, a single intrastriatal injection of rotenone (a) caused a significant nigrostriatal degeneration and loss of dopamine and serotonin from the striatum; (b) elicited cell degeneration in the hippocampus and cortex; (c) induced oxidative stress and neuronal injury (this latter effect of rotenone was not region specific); and (d) the motor deficits (decreased rearing activity) occurred in both limbs.     

Study of the effect of antidepressant drugs and donepezil on aluminum-induced memory impairment and biochemical alterations in rats

Alzheimer’s disease is the leading cause of dementia in the elderly. Depression is a common psychiatric disorder affecting individuals across life span and often arises in the context of pre-dementia, dementia, and Alzheimer’s disease. The present study aimed to investigate the effects of the antidepressant drugs clomipramine (14.2 and 56.9 μmol/kg), fluoxetine (14.5 and 57.8 μmol/kg), and sertraline (14.6 and 58.4 μmol/kg) compared with acetylcholinesterase inhibitor donepezil (12 μmol/kg) on oxidative stress, memory impairment, and depressant-like behavior in a model of Alzheimer’s disease induced by prolonged intraperitoneal administration of aluminum chloride (AlCl₃) (10 mg/kg/day for 60 days) in rats. Results indicated that the latency to find the hidden platform in Morris water maze (MWM) test increased by 100 %, while the immobility duration in forced swimming test (FST) increased by 51 % in AlCl₃-treated rats. The administration of AlCl₃ resulted in increased brain malondialdehyde (MDA) by 58.6 % and nitric oxide (nitrite) concentrations by 71.7 %, while reduced glutathione (GSH) decreased by 35.6 % compared with the vehicle-treated group. Catalase and paraoxonase 1 (PON1) activities in the brain decreased by 41.8 and 18.3 %, respectively. Serum acetylcholinesterase (AChE) increased by 47.8 % and brain butyrylcholinesterase (BuChE) decreased by 23.1 % after AlCl₃ treatment. In AlCl₃-treated rats, memory performance in the MWM test improved following donepezil and the highest dose of clomipramine, fluoxetine, and sertraline. The immobility duration in the FST was decreased by sertraline. Significant decrease in brain MDA occurred after treatment with clomipramine, fluoxetine, and a lower dose of sertraline. Reduced glutathione level increased by donepezil, clomipramine, and 57.8 μmol/kg fluoxetine. The level of nitric oxide decreased by donepezil (42.6 %), clomipramine (45.0 and 62.9 %), fluoxetine (21.9 and 40.9 %), and 14.6 μmol/kg sertraline (28.7 %). Catalase activity was restored by donepezil, fluoxetine, and sertraline and markedly increased by 56.9 μmol/kg clomipramine. Paraoxonase 1 activity was increased by 14.2 μmol/kg clomipramine. BuChE activity was unaltered, but AChE activity was decreased by donepezil, clomipramine, and fluoxetine compared with the AlCl₃ control group. AlCl₃ resulted in neurodegeneration (gliosis), extensive dark neurons with corkscrew dendrites, and degeneration of some Purkinje cell. Following donepezil treatment, no dark neurons were observed, while increased granular cell layer was observed after the administration of a high dose of clomipramine, fluoxetine, or sertraline. The results suggested that in rats treated with AlCl₃, (i) donepezil, sertraline, clomipramine, and fluoxetine improve memory performance; (ii) sertraline was particularly effective in improving depressive-like behavior in this model and might be of value in the treatment of depressive symptoms associated with Alzheimer’s disease; (iii) donepezil, clomipramine, and fluoxetine alleviated oxidative stress; and (iv) neurodegeneration in this model could be modulated by antidepressant drugs and donepezil.     

Potential ultrastructure predicting factors for hepatocellular carcinoma in HCV infected patients

Hepatitis C virus represents one of the rising causes of hepatocellular carcinoma (HCC). Although the early diagnosis of HCC is vital for successful curative treatment, the majority of lesions are diagnosed in an irredeemable phase. This work deals with a comparative ultrastructural study of experimentally gradually induced HCC, surgically resected HCC, and potential premalignant lesions from HCV-infected patients, with the prospect to detect cellular criteria denoting premalignant transformation. Among the main detected pathological changes which are postulated to precede frank HCC: failure of normal hepatocyte regeneration with star shape clonal fragmentation, frequent elucidation of hepatic progenitor cells and Hering canals, hepatocytes of different electron density loaded with small sized rounded monotonous mitochondria, increase junctional complexes bordering bile canaliculi and in between hepatocyte membranes, abundant cellular proteinaceous material with hypertrophied or vesiculated rough endoplasmic reticulum (RER), sequestrated nucleus with proteinaceous granular material or hypertrophied RER, formation of lipolysosomes, large autophagosomes, and micro-vesicular fat deposition.

In conclusion, the present work has visualized new hepatocytic division or regenerative process that mimic splitting or clonal fragmentation that occurs in primitive creature. Also, new observations that may be of value or assist in predicting HCC and identifying the appropriate patient for surveillance have been reported. Moreover, it has pointed to the possible malignant potentiality of liver stem/progenitor cells.

For reliability, the results can be subjected to cohort longitudinal study.     

Molecular identification and phylogenetic analysis of <Emphasis Type="Italic">Wuchereria bancrofti</Emphasis> from human blood samples in Egypt

Lymphatic filariasis (LF) is a serious vector-borne health problem, and Wuchereria bancrofti (W.b) is the major cause of LF worldwide and is focally endemic in Egypt. Identification of filarial infection using traditional morphologic and immunological criteria can be difficult and lead to misdiagnosis. The aim of the present study was molecular detection of W.b in residents in endemic areas in Egypt, sequence variance analysis, and phylogenetic analysis of W.b DNA. Collected blood samples from residents in filariasis endemic areas in five governorates were subjected to semi-nested PCR targeting repeated DNA sequence, for detection of W.b DNA. PCR products were sequenced; subsequently, a phylogenetic analysis of the obtained sequences was performed. Out of 300 blood samples, W.b DNA was identified in 48 (16%). Sequencing analysis confirmed PCR results identifying only W.b species. Sequence alignment and phylogenetic analysis indicated genetically distinct clusters of W.b among the study population. Study results demonstrated that the semi-nested PCR proved to be an effective diagnostic tool for accurate and rapid detection of W.b infections in nano-epidemics and is applicable for samples collected in the daytime as well as the night time. PCR products sequencing and phylogenitic analysis revealed three different nucleotide sequences variants. Further genetic studies of W.b in Egypt and other endemic areas are needed to distinguish related strains and the various ecological as well as drug effects exerted on them to support W.b elimination.     

Inhibited angiogenesis in aging: a role for TIMP-2

Factors responsible for age-associated impairment of angiogenesis are poorly understood. We observed that in aged mice, new fibrovascular tissue within subcutaneous polyvinyl alcohol sponges expressed more tissue inhibitor of metalloproteinases (TIMP)-2 than did corresponding tissue from young mice. In complementary studies in vitro, we utilized young and aged human microvascular endothelial cell lines (hmEC36 and hmEC90, respectively) and compared their morphogenetic capacity within three-dimensional collagen. HmEC90 exhibited poor formation of tubular, capillary-like structures in vitro, diminished expression of active matrix metalloproteinase (MMP)-2, and similar or lesser amounts of MT1-MMP relative to hmEC36. Correspondingly, the MMP inhibitor GM6001 decreased tubulogenesis by hmEC36 to levels observed for hmEC90. In vitro, hmEC90 expressed similar quantities of TIMP-1, but more TIMP-2 than did hmEC36. Accordingly, purified TIMP-2 inhibited tubulogenesis by hmEC36. Collectively, our studies indicate that elevated levels of TIMP-2 modulate decreased angiogenesis in aged tissues, most likely via TIMP-2-mediated inhibition of MMP-2 and MT1-MMP.