AIDS and AIDS-related complex in twenty Zambians with sickle cell anemia

20 Zambians with sickle cell anemia presented with generalized lymphadenopathy and other signs suggestive of the acquired immunodeficiency syndrome or the AIDS-related complex at the Arthur Davison Children's Hospital and the Ndola Central Hospital in Ndola, Zambia. All were found to have anti-HIV antibodies. 3 are known to have died within 10 months of diagnosis. Patients with this sickle cell anemia form a major group at risk for HIV infection through transfusion. The 1st step in prevention is to maintain the health of the patients, so avoiding the need to transfuse blood, and a call is make for the development of Sickle Cell Clinics. Secondly, blood transfusion should be confined to only those patients in danger of dying of anemic heart failure. These 2 steps should be taken, even when blood donors are screened for HIV.     

男性HIV感染/AIDS患者艾滋病相关支原体感染101例分析

目的分析艾滋病相关支原体在人类免疫缺陷病毒(HIV)感染者和获得性免疫缺陷综合征(艾滋病,AIDS)的感染情况。方法以江苏省疾病预防控制中心确认的男性HIV-1感染者为研究对象,经重复横断面调查共收集到101个对象,进行支原体、病毒载量检测及CD4+T细胞计数。结果 2009年调查时,101例中有66例为HIV感染者,35例为AIDS患者,1年后没有新的患者产生。2次调查检测中得到的支原体感染谱相同,均未检测到穿通支原体;生殖支原体的感染率由第1次的35.6%降低至第2次的18.8%(P<0.05),发酵支原体则由第1次调查的6.9%升高至第2次调查的18.8%(P<0.05)。HIV感染者的AIDS相关支原体感染状态发生改变,其病毒载量水平也有变化。结论支原体感染状态的变化与HIV感染者病毒载量具有一定的关联性。但是要确定支原体感染与机体免疫状态的关系,还需更长时间的前瞻性随访研究及体外实验。     

Pharmacological frontiers in the treatment of AIDS dementia

Even in the era of highly active antiretroviral therapy, AIDS dementia remains an important and devastating complication of human immunodeficiency virus (HIV-1) infection. Based on the 1997 AIDS case rate of 56 per 100 000 population in the USA, a reasonable estimated incidence of AIDS dementia is 3-8 per 100000, similar to that of multiple sclerosis. The pharmacology of AIDS dementia has been dominated by antiretroviral therapies, the best studied of which is azidothymidine. New and specific therapies are needed to treat and prevent brain injury in the setting of HIV infection. Rational therapy has been limited by the absence of large, adequate and well-controlled clinical trials using neuroprotective agents or those with disease-modifying potential, as well as by an incomplete understanding of the pathophysiology of AIDS dementia. In this review, a summary of evidence-based hypotheses of HIV-associated brain injury is followed by information on current nonantiretroviral therapeutic trials and their scientific rationale.     

Neurotoxicity and dysfunction of dopaminergic systems associated with AIDS dementia

Infection with the human immunodeficiency virus (HIV) selectively targets the basal ganglia resulting in loss of dopaminergic neurons. Although frequently asymptomatic, some patients may develop signs of dopamine deficiency de novo. Accordingly, they are highly susceptible to drugs that act on dopaminergic systems. Both neuroleptics and psychostimulants may exacerbate these symptoms. Experimental evidence suggests that viral proteins such as gp120 and Tat can cause toxicity to dopaminergic neurons, and this toxicity is synergistic with compounds such as methamphetamine and cocaine that also act on the dopaminergic system. In addition, other neurotransmitters that modulate dopaminergic function, such as glutamate and opioids, may also modify the susceptibility of the dopamine system to HIV. Therefore, a thorough understanding of the mechanisms that lead to this selective neurotoxicity of dopaminergic neurons would also likely lead to the development of therapeutic modalities for patients with HIV dementia.     

Safety and tolerability of zalcitabine (ddC) in patients with AIDS or advanced AIDS-related complex in the European expanded access programme

This international expanded access programme was initiated to provide zalcitabine (o 75 mg three times daily) to patients with AIDS or advanced ARC who had failed, were no longer able to tolerate or were ineligible to receive zidovudine (ZDV). Data are available from 517 patients. No unexpected adverse events occurred during the study with 13.2% of patients discontinuing treatment due to drug-related adverse events. Peripheral neuropathy (PN) was the most common adverse event reported. This was considered to be at least possibly related to zalcitabine in 12.2% of patients, with only 2.3% of patients withdrawing from the study due to zalcitabine-associated PN. Patients with a baseline diagnosis of AIDS and a CD4 count 相似文献   

The feline model of neuroAIDS: understanding the progression towards AIDS dementia

Feline immunodeficiency virus (FIV) is a neurotropic lentivirus that produces a protracted state of immunodeficiency and encephalopathy in the cat. Recent evidence has shown several similarities to the natural progression of human immunodeficiency virus infection (HIV-1) associated degenerative effects on the central and peripheral nervous systems. Similar to HIV-1, FIV-induced encephalopathy neurovirulence is strain dependent, results in progressive immunodeficiency and increasing early peripheral but not brain viral load, preferentially affects the developing nervous system, produces quantifiable behavioural and neurophysiological impairment that is not directly linked to neuronal infectivity, and induces neuronal injury and loss both in vivo and in vitro. This paper highlights the cumulative scientific body of evidence supporting the use of the feline model of neuroAIDS.     

AIDS-related insulin resistance and lipodystrophy syndrome

The recent development of highly active antiretroviral therapy (HAART) has drastically improved the life expectancy of AIDS patients, by reducing infection-related mortality. However, the prolongation of the lives of HIV-1-infected patients and/or the long-term use of novel, potent antiviral agents have generated a score of new problems and complications. Among them is the AIDS-related insulin resistance and lipodystrophy syndrome, which is observed in 30-80% of AIDS patients who are well controlled by HAART. This syndrome is associated with severe metabolic disturbances, such as carbohydrate intolerance/diabetes mellitus and dyslipidemia, which cause atherosclerotic cardiovascular disease. The etiology of this syndrome appears to be multi-factorial; other than the anti-viral drugs, hypercytokinemia and the HIV-1 infection itself, including the virally encoded molecules Vpr and Tat, could contribute to the development of these pathologic changes or increase the vulnerability of patients to the adverse effect of the therapeutic compounds. In this article, we review our current understanding of the pathogenesis and therapeutic approach of this newly emerging AIDS-associated metabolic syndrome.     

Lithium chloride and dilithium carbamyl phosphate: Lithium distribution and toxicity in mice

Dilithium carbamyl phosphate, an antisickling agent, dissociates into lithium cations and carbamyl phosphate dianions in solution. In order to determine which ion is primarily responsible for the toxicity observed at very high doses of dilithium carbamyl phosphate, two groups of 15 mice each were given similar amounts of lithium in twice-daily ip injections for 21, 23, or 30 days. Six of the fifteen mice survived in group A (lithium chloride, 12.9 mEq of Li⁺/kg/day), and 8 of 15 mice survived in group B (dilithium carbamyl phosphate, 13.8 mEq of Li⁺/kg/day). Blood lithium concentrations measured 4–6 hr after an injection averaged 1.7 (±0.7 SD) mEq/liter for each group. Lithium concentrations were measured in 39 samples of tissue or tissue contents from mice in each group. In the surviving animals, lithium ranged from an average of 0.8 – 1.1 mEq/kg in liver to 5–15 mEq/kg in the contents of the lower intestinal tract. Lithium concentrations greater than 15 mEq/kg were often found in the tissues of the nonsurvivors. Hemoglobin carbamylation was 1.0 (±0.3 SD) mol of valine hydantoin/mol of hemoglobin tetramer in mice given dilithium carbamyl phosphate for 21–30 days. This study demonstrates that the toxic effects associated with administration of dilithium carbamyl phosphate appear to be due to the lithium cation rather than the carbamyl phosphate dianion. In all parameters measured, the toxic effects of lithium chloride paralleled those observed when an equivalent amount of lithium was administered as dilithium carbamyl phosphate.     

Lithium and cholinesterase

• 1.1. Preliminary data show that lithium carbonate administered in patients with endogenous depression significantly inhibits serum cholinesterase.
• 2.2. The interaction of lithium with cholinergic system could be envisaged as a possible mechanism of lithium therapeutic action in affective disorders.

     

Targeted inhibition of angiogenic factors in AIDS-related disorders

Immunosuppression associated with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) markedly increases the risk for development of several cancers. Despite its dramatic decrease in frequency after the introduction of highly active antiretroviral therapy (HAART), Kaposi's sarcoma (KS) remains the most common neoplastic manifestation of AIDS. KS is a multicentric angioproliferative tumor, characterized microscopically by spindle cells. KS cells produce and respond to angiogenic factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor-A (VEGF-A). In addition to cellular growth factors, the trans-activator HIV protein Tat plays a major role in the pathogenesis of AIDS-related KS by augmenting the angiogenic activities of bFGF and VEGF-A, and activating the VEGF receptor-2. Viral products from the recently described Kaposi's sarcoma-associated herpesvirus (KSHV) also exhibit potent angiogenic activities. KSHV is consistently associated with KS and two lymphoproliferative disorders, primary effusion lymphoma (PEL) and the plasma cell variant of multicentric Castleman's disease (MCD). Several viral genes may contribute to the phenotype of PEL and MCD: among them, a viral homologue of interleukin-6 (vIL-6) has attracted much attention due to its potential to stimulate B cell growth and accelerate angiogenesis via VEGF-A induction. In this review, we summarize current knowledge and hypothesis regarding the cellular and viral angiogenic factors involved in the pathogeneses of AIDS-related malignancies, and discuss novel therapeutic strategies based on targeting pro-angiogenic factors.     

Cerebral arachidonate cascade in dementia: Alzheimer's disease and vascular dementia

Phospholipase A(2) (PLA(2)), cyclooxygenase (COX) and prostaglandin (PG) synthase are enzymes involved in arachidonate cascade. PLA(2) liberates arachidonic acid (AA) from cell membrane lipids. COX oxidizes AA to PGG(2) followed by an endoperoxidase reaction that converts PGG(2) into PGH(2). PGs are generated from astrocytes, microglial cells and neurons in the central nervous system, and are altered in the brain of demented patients. Dementia is principally diagnosed into Alzheimer's disease (AD) and vascular dementia (VaD). In older patients, the brain lesions associated with each pathological process often occur together. Regional brain microvascular abnormalities appear before cognitive decline and neurodegeneration. The coexistence of AD and VaD pathology is often termed mixed dementia. AD and VaD brain lesions interact in important ways to decline cognition, suggesting common pathways of the two neurological diseases. Arachidonate cascade is one of the converged intracellular signal transductions between AD and VaD. PLA(2) from mammalian sources are classified as secreted (sPLA(2)), Ca(2+)-dependent, cytosolic (cPLA(2)) and Ca(2+)-independent cytosolic PLA(2) (iPLA(2)). PLA(2) activity can be regulated by calcium, by phosphorylation, and by agonists binding to G-protein-coupled receptors. cPLA(2) is upregulalted in AD, but iPLA(2) is downregulated. On the other hand, sPLA(2) is increased in animal models for VaD. COX-2 is induced and PGD(2) are elevated in both AD and VaD. This review presents evidences for central roles of PLA(2)s, COXs and PGs in the dementia.     

Viral and cellular cytokines as therapeutic targets in AIDS-related lymphoproliferative disorders

Since the advent of highly active antiretroviral therapy (HAART) and its widespread use, the incidence of AIDS-defining illnesses has decreased dramatically, leading to a much longer survival of patients. Despite some exciting new leads, non-Hodgkin's lymphoma (NHL) remains a fatal malignancy for the vast majority of patients with acquired immunodeficiency syndrome (AIDS). Multiple molecular pathways appear to operate in AIDS lymphomagenesis and some may preferentially be associated with specific malignant histopathologic categories or anatomic sites of origin. AIDS-associated lymphomas share several features, including B-cell lineage derivation, diffuse aggressive histology, and frequent origin from or involvement of extranodal sites. Recently, high-grade primary effusion lymphomas (PEL) have been reported in patients with advanced AIDS. PEL is recognized as a distinct clinicopathologic entity associated with Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8 (HHV-8). KSHV genes are likely to contribute to the neoplastic phenotype of PEL cells that require cytokines and factors from the host or encoded by the virus for growth in vivo. KSHV is also thought to dramatically affect the incidence, type, and course of multicentric Castleman's disease, another lymphoproliferative disorder over-represented in patients with AIDS. This review summarizes the current knowledge of autocrine growth factor loops and angiogenic factors that are involved in the pathogenesis of KSHV-related lymphoproliferative disorders in AIDS. Deregulated cytokines may represent potential targets of novel therapeutic strategies.     

Lithium and weight gain

Lithium prophylaxis leads to weight gain in a high proportion of patients treated, with up to a quarter becoming clinically obese. This can have detrimental effects on compliance and is also a health risk. The mechanism of such lithium-induced weight gain is unknown, but increased calorie intake, particularly in the form of high calorie drinks, has been implicated. Remedial steps such as adjusting the lithium dose and giving appropriate dietary advice should be taken at the first sign of weight gain.     

Lithium in psychiatric therapy

Summary Lithium therapy is effective against manic phases of the manic-depressive psychosis; in protracted or frequently recurring mania it seems to offer advantages over other available therapies. Lithium salts are administered orally; they may be given alone or as a maintenance treatment after electric convulsive therapy.Lithium is potentially toxic, and overdosage may lead to injury of the kidney tubules. A high sodium intake accelerates renal elimination of lithium and serves to protect the organism against intoxication.Patients suffering from renal or cardiac disease should not be given lithium. In patients receiving lithium the dosage must be regulated according to individual tolerance, and one must make sure that the sodium intake is sufficient and remains sufficient. The patients should be supervised clinically and biochemically.     

Lithium and drug interactions

The mutual enhancement of the side effects of muscular tremor and rigidity caused by lithium and neuroleptic drugs should be recognised. However, at present the 'case' for a neuroleptic-lithium interaction producing severe organic brain syndrome is arguably weak; in the absence of standardised sampling for monitoring lithium serum concentrations such reports may simply reflect 'pure' lithium intoxication rather than a drug interaction. Certainly it seems unwarranted in this connection to ascribe specific properties to haloperidol. A potentially high risk of interaction should be recognised between lithium and natriuretic diuretics, and other drugs and therapeutic measures affecting sodium balance. Such interactions may disturb stable treatment monitoring and give rise to the start of self-increasing lithium intoxication. The practical clinical importance of lithium interactions with neuromuscular blocking agents, phenytoin, carbamazepine, iodide salts and methyldopa is only weakly supported by the data available at this time. However, if simple prophylactic measures are available when such drugs are to be used in patients receiving lithium, for example temporary withdrawal of lithium, it may be prudent to take such steps.