HIV-associated lymphoma: promising new results, but with toxicity

Treatment of HIV-associated non-Hodgkin lymphoma with rituximab plus infusional cyclophosphamide, doxorubicin, and etoposide resulted in high complete remission and 2-year failure free and overall survival rates but a high rate of infection.     

Natural compounds and extracts from Mexican medicinal plants with anti-leishmaniasis activity: An update

Leishmaniasis is considered as an emerging, uncontrolled disease and is endemic in 98 countries. Annually, about 2 million cases of cutaneous and 500000 cases of visceraltype leishmaniasis are recorded and 60000 persons died from the disease. In Mexico,cutaneous leishmaniasis is known as chiclero's ulcer and is reported in 22 states, it is considered as a health problem. For its treatment, pentavalent antimonial drugs are administered. These drugs cause severe side effects, are costly. Drug-resistant cases have been reported and have been developing for over 70 years. One alternative to the drugs that are currently available is to find active molecules in medicinal plants. Dihydrocorynantheine, corynantheine and corynantheidine are active against Leishmania major,while harmane, pleiocarpin, buchtienin, luteolin and quercetin are active against Leishmania donovani. In Mexico, about 20 medicinal plants have been evaluated against Leishmania mexicana, among which the most active are Tridax procumbens, Lonchocarpus xuul and Pentalinon andrieuxii. From these plants, active compounds with IC_(50)≤30 mg/mL or m M have been isolated, such as 3(S)-16,17-didehydrofalcarinol or Oxylipin, cholestra-4,20,24-trien-3-one or pentalinosterol, 24-methylcholest-4-24(28)-dien-3-one, cholest-4-en-3-one, 6,7-dihydroneridie-none, neridienone, cholest-5,20,24-trien-3β-ol, and isocordoin. Today, only pentalinonsterol has been synthesized and assayed in the visceral leishmaniasis experimental model using BALB/c mice infected with Leishmania donovani. Liposome formulation of this compound administered by intravenous route at 2.5 mg/kg showed a significant reduction of parasite load in mouse liver and spleen.     

Retinoids and interferon: a new promising combination?

The retinoids: all-transretinoic acid (tretinoin), 13-cis retinoic acid (isotretinoin) and the aromatic retinoids etretinate and acitretin have a preventive and therapeutic effect on chemically-induced tumours. Clinically, retinoids have shown variable effectiveness in therapy and/or prevention of oncological diseases of skin, head and neck, lung, bladder, vulva and bone marrow, With a few exceptions, monotherapy with retinoids has not been satisfactory. Similarly, monotherapy with interferon alpha has been used successfully only for some specific indications. Retinoids have a marked differentiation-inducing effect which may contribute to their therapeutic effect. Experiments were carried out in transformed cell lines to test the combination of retinoids with interferon alpha and other cytokines on differentiation. In HL-60 cells, an acute promyelocytic leukaemia cell line, induction of differentiation was determined by induction of an oxidative burst potential. Retinoids showed the following order of activity: tretinoin > isotretinoin > acitretin. Cytokines had no differentiation-inducing effect by themselves. However, the addition of the following cytokines to retinoids potentiated the retinoid-induced differentiation: IFNα, IFNβ, IFNγ, TNFα, G-CSF, IL-1α and IL-4. In experiments with HL-60 or other cell lines, the pattern of differentiation-induction was always dependent on the particular retinoid/cytokine combination. IFNα provoked a marked potentiation of retinoid-induced differentiation. The combination of the antipro-liferative and differentiation-inducing effect of the retinoids together with the antiproliferative, immunostimulatory and differentiation-potentiating effects of IFNα suggests that this combination might be a particularly promising treatment for neoplastic diseases.     

Magnetic resonance colonography: A promising new technique

Colorectal carcinoma is still the second leading cause of cancer-related death, although it arises mostly from benign adenomas. Numerous screening methods are available, but none of them is accepted as ideal. Ultrafast three-dimensional data sets acquired by cross-sectional imaging modalities (CT or magnetic resonance [MR]) in combination with new post-processing modes, known as virtual colonoscopy, have led to a new discussion of screening tests for colorectal cancer. Recently published results indicate a high sensitivity for CT colonography and for MR-based colonography (MRC), with detection rates of greater than 90% for colorectal lesions greater than 10 mm in size. Three-dimensional data acquisition for MRC is performed in less than 1 minute, and no severe complications have been reported. The main advantages of MRC are the lack of ionizing radiation, the low risk of the procedure, and low patient discomfort. MRC has become an attractive diagnostic procedure for colorectal lesions that can also be used as a screening method.     

Evolving concepts in functional gastrointestinal disorders: promising directions for novel pharmaceutical treatments

In recent years there has been an increasing appreciation of the complexity of functional gastrointestinal disorders. These represent a spectrum of conditions which may affect any part of the gastrointestinal tract in which there appears to be dysregulation of visceral function and afferent sensation and a strong association with emotional factors and stress. There is a clear psychological dimension, with up to 60% of irritable bowel syndrome (IBS) patients reported to have psychological co-morbidities and altered pain perception is also common in comparison with control populations. The role of the enteric nervous system, the sensory pathways and the brain as well as the influence of the latter on sympathetic and parasympathetic outflow have likewise attracted increasing interest and have led to exciting new methods to study their complex interactions. The concept of low-grade inflammation, such as might occur after infection, acting as a trigger for neuromuscular dysfunction has also led to the broad integrative hypotheses that help to explain the biopsychosocial dimensions seen in functional gastrointestinal disease. The multi-component model places a major emphasis on neurogastroenterology and enteric and neuro-immune interactions where new approaches to pharmacotherapy lie. Drugs may affect motility, visceral sensation and other aspects of gut function such as secretion or absorption. More particularly, however, has been the search for and attempts to influence important mediators of these primary gut functions. Such targets include serotonin and selected 5-HT receptors, which are involved in gut motility, visceral sensation and other aspects of gut function, CCK receptors which are involved in the mediation of pain in the gut and nociception in the CNS, opioid receptors involved in pain in the brain, spinal cord and periphery, muscarinic M3-receptors, substance P and neurokinin A and B receptors which are involved in motor adaptation and pain transmission in association with inflammation, gabba receptors involved in nociception and cannabinoid receptors which are involved in the control of acetyl choline release in the gut. With a better understanding of the structures and pathways involved in visceral perception and hyperalgesia, in the CNS, spinal cord and the gut and new pharmacological tools we will be better able to elucidate the neuropharmacology of visceral perception and its relationship to gut dysfunction. It is likely that there will be multiple therapeutic options based on the spectrum of abnormalities capable of causing the spectrum of symptoms of functional gastrointestinal disorders in any individual patient.     

Gastroesophageal reflux disease: new treatments

The primary therapeutic endpoint for patients with gastroesophageal reflux disease is complete relief of symptoms and improvement in quality of life. The withdrawal of cisapride has created a vacuum in the prokinetic market, with few promising drugs in the pipeline. Reflux inhibitors are being considered for clinical trials, but as of yet are unavailable. Proton pump inhibitors (PPIs) continue to be the backbone of therapy for acid suppression, providing excellent relief of symptoms and healing of erosive esophagitis. Isomeric technology with esomeprazole as the prototype represents an advance in PPI pharmacology. Antireflux surgery is now more patient-friendly, with shorter hospitalization and less major morbidity compared to open fundoplication, but surgery is at best equal to medical therapy when optimal doses of antisecretory therapy are used. Two endoscopic procedures were recently approved by the U.S. Food and Drug Administration for treatment of gastroesophageal reflux disease: radiofrequency energy delivery to the gastroesophageal junction, and transoral flexible endoscopic suturing. These techniques should be used selectively until we have more data and until results are compared to the safe and highly effective medical therapies.     

Acute pancreatitis and organ failure: Pathophysiology,natural history,and management strategies

Acute pancreatitis is a common condition that carries a significant risk of morbidity and mortality. It is characterized by intra-acinar cell activation of digestive enzymes and a subsequent systemic inflammatory response governed by the release of proinflammatory cytokines. In 80% of patients the disease runs a self-limiting course, but in the rest, pancreatic necrosis and systemic organ failure carry a mortality rate of up to 40%. The key to management is early identification of the patients liable to have a severe attack and require treatment in a high-dependency or critical-care setting by a specialist team. In gallstone-induced pancreatitis, early removal of ductal calculi by endoscopic sphincterotomy is indicated. The use of prophylactic antibiotics to prevent the infection of pancreatic necrosis remains controversial, but once established, infected necrosis must be removed. Although a number of techniques to accomplish this end have been described, minimally invasive techniques are gaining in popularity.     

Septic arthritis: practical diagnosis and new treatments

Septic arthritis remains a major challenge to physicians because the increasing frequency of certain microorganisms to become in antibiotic-resistant and persistent difficulties regarding both early diagnostics and proper treatment of subjects with joint infections. This paper will review current diagnostics test and their contribution to the rapid evaluation of joint infection. Importantly, updated therapeutic suggestions will be presented which, when appropriately applied, should diminish the risks of sequelae following infectious arthritis.     

Oral anticoagulants and medicinal plants. An emerging interaction

The consumption of herbal medicines is increasing steadily throughout the world, although to our knowledge there are neither studies on their effectiveness nor controls over the quality and safety of these preparations. Considered "food integrators", these preparations are marketed without restriction. It is a common notion that natural therapy has neither side nor toxic effects: allergic reactions, direct toxic effects or those due to contamination, carcinogenicity, mutagenicity, and heavy metal toxicity have been reported as adverse events caused by herbs. Rather than replacing traditional therapy, most herbal medical treatment is used in conjunction with it. Also, the attending physician is generally not informed that the patient is using herbs. Because Passionflower, hydroalcoholic extracts, Juniper and Verbena officinalis supply variable quantities of vitamin K, they can lessen the effect of oral anticoagulant therapy. Ganoderma Japonicum, Papaw, Salvia miltiorrhiza, Ginseng, Devil's claw, Garlic, Quinine, Ginkgo, Ginger, Red Clover and Horse-Chestnut reinforce warfarin action by heterogeneous mechanisms. They should thus not be used in patients on oral anticoagulant and/or antiplatelet therapy. The scientific community must take into account the adverse events caused by interaction between herbal medicine and conventional therapy, and patients must be informed of the dangers of these preparations. If a bleeding event occurs or the quality of anticoagulant therapy is poor, the clinician should consider the possibility of interaction between conventional therapy and herbal medicine that the patient has neglected to mention he is taking.     

Metabolic engineering of medicinal plants: transgenic Atropa belladonna with an improved alkaloid composition.

The tropane alkaloid scopolamine is a medicinally important anticholinergic drug present in several solanaceous plants. Hyoscyamine 6 beta-hydroxylase (EC 1.14.11.11) catalyzes the oxidative reactions in the biosynthetic pathway leading from hyoscyamine to scopolamine. We introduced the hydroxylase gene from Hyoscyamus niger under the control of the cauliflower mosaic virus 35S promoter into hyoscyamine-rich Atropa belladonna by the use of an Agrobacterium-mediated transformation system. A transgenic plant that constitutively and strongly expressed the transgene was selected, first by screening for kanamycin resistance and then by immunoscreening leaf samples with an antibody specific for the hydroxylase. In the primary transformant and its selfed progeny that inherited the transgene, the alkaloid contents of the leaf and stem were almost exclusively scopolamine. Such metabolically engineered plants should prove useful as breeding materials for obtaining improved medicinal components.     

Natural variability of essential oil and antioxidants in the medicinal plant Turnera diffusa

Objective:To evaluate differences in yield and composition of the essential oil and antioxidant contents in T.diffusa plants from localities in central region of Tamaulipas.Methods:Samples were collected in Tamaulipas,Mexico in the arid zone.Essential oil was obtained through steam distillation and analyzed using GC-MS.Polyphenol contents,antioxidant activities using ABTS and ferric reducing antioxidant power(FRAP) methods also were evaluated.Results:A total of 21 compunds were identified in the essential oils;nevertheless,only Eucalyptol,1,4-Methanocycloocta[d]pyridazine,1,4,4a,5,6,9,10,10a-octahydro-11,11-dimethyl-,(1à,4à,4aà,10aà) y Ethanone,1-(1,3-dimethyl-3-cyclohexen-1-yl) were detected in the three sites.Highest contents were registered in the sample from Padrón y Juárez with phenolic content of 33.85 mg GAE/g of dry material and antioxidant activities with ABTS 72.32% and with FRAP 21.33 mg GAE/g of dry material.Statistical differences were observed in essential oil,phenolics and antioxidants contents between populations.Conclusions:Results suggest that climatic differences and origin influence the phytochemicals in the medicinal plant T.diffusa,and thus,it is worth to consider such effects for industrial and medicinal purposes.     

Brucellosis: Atypical Presentation with Abdominal Pain

A patient with an atypical presentation of brucellosis is reported. The principal complaints of fever and abdominal pain did not initially suggest this diagnosis although a careful social history revealed the patient to be at risk of developing this infrequently reported infection. The gastrointestinal and hepatic manifestations of brucellosis are reviewed.     

Orphan diseases: evaluations of new treatments

The new treatments of orphan diseases must be assessed according to the methodologic rules of therapeutic trials, in order to ensure clinically and statistically significant evaluations: randomized controled trials, single primary end-point, statistically significant and clinically relevant efficience. Although these rules may be relaxed in orphan diseases, they have to maintain the standard of therapeutic efficiency.