Thymosins and anti-thymosins: properties and clinical applications

For years, scientists have searched for ways to trigger the body's own defenses against cancer and other diseases associated with abnormal immunity. This search has led to the discovery of a number of important new biological and chemical substances that augment, direct or restore many of the normal defenses of the body. These substances are in essence the natural drugs of the body that endow us with immunity and resistance to disease. Now called biological response modifiers (BRMs), most of these 'new medicines', such as thymosins, lymphokines, and interferons, occur naturally in the body, while others, synthetic immunomodulators and thymomimetic agents (drugs that mimic thymic function) have been created in the laboratory. Previously, therapeutic drug development in this area relied upon chemical synthesis or introduction of bacterial adjuvants, or modified viral compounds and substances, which were foreign to the body. Therefore, they did not and do not rely upon or use the body's natural immune and biological response systems for protection against disease, function and response to the environment. Although scientists have known about BRMs for years, isolating and purifying them so that they could be used to treat diseases has been extremely difficult. Many of these substances, such as the lymphokines, occur in the body in minute amounts and normally do not circulate in the blood. The development of new technologies for isolation and large scale synthesis, e.g. solid phase peptide synthesis, high-pressure liquid chromatography microsequencing and genetic engineering, has now permitted scientists to isolate, purify, and synthesize BRMs in sufficiently large quantities to allow human clinical trials. In this paper we will focus on the potential clinical applications of the thymosins and anti-thymosins.     

Monocrotophos-Induced Mass Mortality of Swainson's Hawks in Argentina, 1995–96

Swainson's hawks (Buteo swainsoni) were observed in the grasslands (pampas) of Argentina during the austral summer of 1995–96. Widespread agrochemical use to control insects had a profound effect on flocks of hawks foraging on grasshoppers and caterpillars throughout the pampas. We describe 19 mortality incidents and an estimated 5,095 dead hawks. Forensic analysis indicated that the organophosphate insecticide monocrotophos was responsible for the deaths at six separate sites, accounting for over 4,000 of the mortalities. Brain cholinesterase was lethally inhibited (>95%) and monocrotophos residues (n=31/45, mean=0.20 ppm, range 0.05–1.08 ppm) were found in the contents of the gastrointestinal tract. No other insecticide residues were found. Sample analyses, combined with interviews with farmers, indicated that monocrotophos was responsible for deaths at 17 of 19 mortality incidents.Novartis Crop Protection AG, Residue Analysis     

Reliability of quantitative sudomotor axon reflex testing and quantitative sensory testing in neuropathy of impaired glucose regulation

Reproducible neurophysiologic testing paradigms are critical for multicenter studies of neuropathy associated with impaired glucose regulation (IGR), yet the best methodologies and endpoints remain to be established. This study evaluates the reproducibility of neurophysiologic tests within a multicenter research setting. Twenty‐three participants with neuropathy and IGR were recruited from two study sites. The reproducibility of quantitative sudomotor axon reflex test (QSART) and quantitative sensory test (QST) (using the CASE IV system) was determined in a subset of patients at two sessions, and it was calculated from intraclass correlation coefficients (ICCs). QST (cold detection threshold: ICC = 0.80; vibration detection threshold: ICC = 0.75) was more reproducible than QSART (ICC foot = 0.52). The performance of multiple tests in one setting did not improve reproducibility of QST. QST reproducibility in our IGR patients was similar to reports of other studies. QSART reproducibility was significantly lower than QST. In this group of patients, the reproducibility of QSART was unacceptable for use as a secondary endpoint measure in clinical research trials. Muscle Nerve, 2008     

Anti-desmoglein 1 antibodies in healthy related and unrelated subjects and patients with pemphigus foliaceus in endemic and non-endemic areas from Tunisia

Background  Pemphigus foliaceus is an autoimmune blistering skin disease characterized by the production of pathogenic IgG autoantibodies directed against desmoglein 1.
Aim  To determine the prevalence of anti-desmoglein 1 antibodies in healthy subjects and their distribution in the different regions of Tunisia and to better identify endemic areas of pemphigus foliaceus.
Methods  We tested, by enzyme-linked immunoserbent assay, sera of 270 normal subjects recruited from different Tunisian areas and 203 related healthy relatives to 90 Tunisian pemphigus foliaceus patients.
Results  Seventy-six patients (84.4%), 20 healthy controls (7.4%), and 32 relatives (15.76%) had anti-desmoglein 1 antibodies. In southern regions where pemphigus foliaceus is associated with a significant sex ratio imbalance (9 female : 1 male in the south vs. 2.3 : 1 in the north) and a lower mean age of disease onset (33.5 in the south vs. 45 years in the north), a higher prevalence of anti-desmoglein 1 antibodies in healthy controls was observed (9.23% vs. 5.71% in the north). Interestingly, the highest prevalence of anti-desmoglein 1 antibodies in healthy relatives (up to 22%) was observed in the most rural southern localities. More than half anti-desmoglein 1–positive healthy controls were living in rural conditions with farming as occupation, which suggests that this activity may expose the subjects to particular environmental conditions.
Conclusion  These results show that the endemic features of Tunisian pemphigus foliaceus are focused in these southern areas more than in other areas and that both environmental and genetic factors contribute to the disease.

Conflicts of interest

None declared.     

Ein Beitrag zur Lehre von der Bedeutung der Insel für die Sprache und der linken Hemisphäre für das linksseitige Tasten

Ohne Zusammenfassung     

Functional outcomes following medical intensive care

This study describes the long-term functional outcomes of a medical and coronary care ICU population. Baseline and 1-yr follow-up data were collected prospectively from all 2213 patients admitted during a 2-yr period. Patients were stratified into three groups based on their preadmission functional status: active (n = 917), sedentary (n = 1017), or severely limited (n = 279). Those with severe functional limitation before admission were twice as likely to undergo major interventions (p less than .005). This group also had a significantly (p less than .001) higher mortality and incurred significantly (p less than .01) higher hospital charges than the other two groups, even though hospital lengths of stay were similar. Finally, cumulative mortality was significantly (p less than .001) greater for the severely limited patients: 33% expired in the ICU, 42% died while still in the hospital, and 63% died after discharge. Most survivors regained their preadmission functional status, with 60% of the previously employed returning to work. However, even for hospital survivors, mortality was high and was related to prior functional status: active 7%, sedentary 20%, severely impaired 37%.     

Aspirin and thymosin increase interleukin-2 and interferon-gamma production by human peripheral blood lymphocytes

Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) have recently been added to the arsenal of synthetic biological response modifiers with important immunomodulatory activities. In this paper we have assessed the effects of acetylsalicylic acid (aspirin), thymosin alpha and thymosin fraction 5 (TF5), a partially purified calf thymic preparation, on production of IFN-gamma in vitro. Stimulation by oral aspirin of IL-2 and IFN-gamma production by peripheral blood lymphocytes (PBLs) was also studied in healthy human volunteers. Aspirin, thymosin alpha 1 and TF5 were all observed to enhance phytohemagglutinin (PHA)-stimulated production of IFN-gamma. Peak IFN-gamma production by PHA-stimulated PBLs was observed after 24 h of incubation with TF5 and after 72 h with aspirin. Stimulation by aspirin and TF5 required the presence of macrophages, and was additive and dose-dependent. The additive effects of aspirin and TF5 suggest that these agents act by different mechanisms. Oral administration of aspirin in normal volunteers significantly enhanced production of both IFN-gamma and IL-2. PHA-stimulated IFN-gamma production was greatest 24 h after aspirin ingestion; in contrast, IL-2 production was optimal 10 h after aspirin ingestion. These observations suggest that oral aspirin is an effective biological response modifier in humans and raise the possibility of a novel combination approach to immunomodulation involving cyclooxygenase inhibitors and thymosins.     

Magnetic resonance imaging of the posterior fossa in ocular motility disorders--four case studies

The superiority of magnetic resonance imaging (MRI) of the posterior fossa over x-ray computed tomography is demonstrated by four patients with neuro-ophthalmologic disorders. Advantages of this technique include lack of ionizing radiation, direct multiplanar imaging, increased sensitivity to pathology, increased tissue contrast, and no known adverse effects. It is concluded that MR, when available, should be the imaging modality of choice in patients with neuro-ophthalmologic disorders of suspected brainstem origin.