Chemical derivatization as a strategy to enhance detectability of agents used in cancer management

The bioanalysis of drugs used in the management of cancer is often complicated by the lack of selectivity and sensitivity. Chemical derivatization of these drugs prior to their chromatographic analysis represents a viable strategy to improve chromatographic resolution and to enhance detectability. This review provides examples of how this approach can meet these objectives. Derivatization of racemic cyclophosphamide with a chiral acylating agent, following hydroxyalkylation to introduce a reactive centre into the molecule, provides the basis for its stereospecific analysis. The analysis of dianhydrogalactitol is described, in which diethyldithiocarbamate is used as a nucleophilic derivatizing agent that improves chromatographic behaviour and analytical sensitivity. The final example that is described is the design and preparation of improved fluorogenic reagents (o-phthalaldehyde analogues) for the derivatization of peptides and application of these reagents to the trace analysis of leu-enkephalin in plasma.     

Heterogeneity of human basophils and mast cells in response to muscle relaxants

We investigated thein vitro effects of increasing concentrations (10^–5–10^–3 M) of four muscle relaxants (succinylcholine, d-tubocurarine, vecuronium and atracurium) on histamine release (HR) from human peripheral blood basophils and mast cells isolated from lung parenchyma (HLMC) and skin tissues (HSMC). Basophils released less than 5% of their histamine content when incubated with any one of the muscle relaxants. In contrast, mast cells showed a marked heterogeneity in their response. Succinylcholine did not induce HR from any type of mast cell, and only high concentrations of d-tubocurarine (10^–3 M) caused HR from HSMC and HLMC. Vecuronium concentration-dependently induced HR from HLMC and HSMC. Atracurium concentration-dependently caused marked HR from HLMC and HSMC up to a maximum of 46.2±15.1% and 30.6±6.0%, respectively. From both HLMC and HSMC HR caused by atracurium and vecuronium was extremely rapid (t_1/2<1 min).=" the=" releasing=" activity=" of=" atracurium=" and=" vecuronium=" on=" hlmc=" and=" hsmc=" was=" reduced,=" but=" not=" abolished,=" by=" lowering=" the=" temperature=" of=" the=" incubation=" buffer=" to=" 22°c=" and=" 4°c.=" these=" results=" confirm=" that=" there=" are=" functional=" differences=" between=" human=" basophils=" and=" mast=" cells=" and=" among=" mast=" cells=" isolated=" from=" different=" anatomical=" sites=" in=" response=" to=" the=" muscle=" relaxants=">     

Relative sensitivity of four noninvasive methods in assessing systolic cardiovascular effects of isoproterenol in healthy volunteers.

STUDY OBJECTIVE: The study was performed to evaluate the relative sensitivity of various noninvasive methods to detect and describe the systolic cardiovascular effects of stepwise increasing doses of isoproterenol: two-dimensional left ventricular echocardiography (main variable, ejection fraction), ACVF (attenuation compensated volume flow)--dual-beam Doppler echoaortography (time-averaged mean velocity), electrical impedance cardiography [(dZ/dtmax)/RZ index], and systolic time intervals from mechanocardiography (PEP and QS2c). METHODS: Isoproterenol was administered by constant rate intravenous infusion in consecutive steps of 0.1, 0.2, 0.4, 0.75, and 1.5 micrograms/min (each for 15 minutes). Saline control infusions were given in analog fashion. The treatments (isoproterenol and saline solution) were administered in a period-balanced two-way crossover design with randomly allocated sequences. The subjects, observers, and analysts were blinded to the treatment protocol. Study subjects were 10 healthy male volunteers (age range, 23 to 31 years; mean age, 26.6 years). RESULTS: Compared with saline solution, isoproterenol caused a dose-related increase in ejection fraction, (dz/dt)/RZ index, and time-averaged mean velocity and a dose-related shortening of PEP and QS2c. The responses are congruent with an enhancement of cardiac systolic performance caused by a positive inotropic stimulation and an afterload reduction ("inodilatory" response). The effects on systolic time intervals reached statistical significance (alpha = 0.05) at the first isoproterenol dose step, the effects on the impedance cardiography and the Doppler echoaortography variables reached statistical significance at the second dose step, and the effects on the two-dimensional echocardiography reached statistical significance at the third dose step. CONCLUSIONS: All methods allowed to detect isoproterenol-related changes. Systolic time intervals were the most sensitive, followed by impedance cardiography, ACVF--dual-beam Doppler echoaortography, and two-dimensional echocardiography. The practical convenience and high sensitivity of the systolic time intervals makes them suitable to evaluate investigational systolic inodilatory changes in humans.     

Thyroid albumin originates from blood.

Iodoalbumin has been found in the goiter of Dutch goats with a thyroglobulin synthesis defect. Immunohistochemical studies showed that in the goiter the percentage of follicles containing albumin was higher than that in normal thyroid glands. In the albumin-containing follicles of normal and goitrous glands, transferrin and immunoglobulin G could be found. Also, between the epithelial cells, serum proteins were detected. These results indicate intercellular passage of serum proteins. After in vivo labeling with 125I, goiter slices were incubated with [3H] leucine. Purified 125I-containing albumin did not contain [3H]leucine, while thyroglobulin antigens were double labeled. Cyanogen bromide treatment of albumin out of the goiter and of serum albumin gave comparable cleavage patterns, indicating that no great differences in amino acid composition, especially methionine, exist. In total RNA from goiter, no albumin mRNA could be detected after blotting and hybridization with goat albumin cDNA. Also, the polymerase chain reaction method with albumin DNA primers was unable to detect any albumin mRNA in normal and goitrous glands of goats. From these results we conclude that "thyralbumin" originates from blood and is not synthesized by the thyroid gland.     

Naevus follicularis keratosus: clinical aspects, histology and histogenesis]

The clinical, histological and histogenetic aspects of naevus follicularis keratosus (NFK) ("naevus comedonicus") are reported. Clinically, NFK appears mostly as linear and unilateral groups of dark comedo-like plugs. Clinical forms include variants with minimal and distinctive deviations from the basic form. Recurrent inflammation is not mandatory. Histological examination reveals keratin-filled infundibula, with granular layers that are always present but though not always equally obvious. This finding corresponds to the mode of keratinization in the follicular infundibulum. Overall, the findings are indicative of a harmartoma of the follicular infundibulum with additional rudimentary sebaceous glands.     

Characteristics of the demand for cranial computerized tomography: reasons and costs of the exam]

It was reviewed a series of 2860 cerebral computed tomography (CCT) in order to compare the main reasons at referral to investigation with the CCT results and the costs with normal and abnormal CCT. It was also studied the age and sex of the patients. Data were collected from one out of three diagnostic centers in Salvador, Brasil, for a three years period. The 2860 CCT exclude all investigation carried out for the follow-up of a previously diagnosed abnormality. CCT abnormalities were detected in 1152 (40.3%). The following reasons showed the highest proportion of abnormal CCT, for males and females respectively: demential syndrome (91.7 and 83.3%); cerebrovascular accidents (85.1 and 73.6%); infectious and parasitary diseases (76.5 and 78.6%); tumors (65.8 and 55.4%); and head injuries, 63.6% for males. In the female group, 65.0% of the CCT were normal, in a range of 65.0 to 80.0% for the age groups under 54 years old. In the male group, the highest proportion of normal CCT was found in the age groups: 25-34 (68.4%), < 15 (62.9%) and 35-44 (62.7%). The most common reasons for normal CCT for males and females were: headache (81.3 and 87.5%); dizziness/vertigo (79.3 and 78.6%); seizures (67.3 and 70.0%); psychomotor deficiency (72.0 and 67.7%) and "endocrine disorders", 75.0% for each sex. The highest proportion of normal CCT (65.3%) was requested by medical "convenios". The cost with normal CCT reached US$565,225 and with the abnormal ones, US$381,247. Costs with normal CCT were 2.2 higher for medical "convenios" as compared to those of the National Institute of Security requests and 2.8 more than those of private medicine.     

Peripheral facial paralysis in Petropolis]

The author presents 83 cases of "a frigore" peripheral facial palsy, occurred in the mountain city of Petropolis which has characteristics such as a tropical climate without any traces of a dry season and an average temperature of 50 degrees F to 73.5 degrees F. The author relates them with virus infections which appear within a year period. Fifty six patients belong to his clinic and have a follow up, while other 25 patients proceed from another clinics and from them he only has reports on sex, age, side of palsy and the beginning of illness. He shows that the largest number of cases occurred along the months of May, August, September and October. Season distribution for southern hemisphere is analysed. He also considers etiology, incidence, prevalence, treatment and results on patients studied.     

Pineal "synaptic" ribbons evolution over a 24 hour period during two different photoluminous seasons, a comparative and statistical analysis.

A comparative statistical analysis of "synaptic ribbons" evolution over a 24 hour period during two different photoluminous seasons (September, and winter) is carried out. Seventy male rats were used. Statistical analysis involved the Kolmogorov-Smirnov test, variance analysis, the Student t-test and Pearson's correlation test. The results show that "synaptic ribbons" evolve during the circadian phase and through two different seasons, with a clear and marked influence of point-time (p < 0.0001) and season (p < 0.0001).     

EEG and Seizures in Children with Hemolytic–Uremic Syndrome

The EEG results of 11 children, ages 1-15 years, who presented with hemolytic-uremic syndrome complicated by seizures 3-10 days after the prodrome were studied. In four children who experienced generalized tonic-clonic seizures, the EEGs demonstrated diffuse delta slowing with no focality. All recovered without neurological deficit or a residual seizure disorder. Of seven children who experienced partial seizures, six had structural lesions on cranial computed tomography and residual focal neurological deficits with epilepsy. The EEGs in two patients revealed focal spikes and slowing consistent with the lateralization of the partial seizures, in four it was characterized by atypical "burst suppression," and in one showed epochs of high-amplitude delta slowing alternating with generalized suppression. Although episodic and generalized burst suppression is usually regarded as a grave prognostic indicator, all four subjects recovered.     

The psychiatric services in cremona: A case study of the Italian reform law

Italy's mental health law of 1978 provided for the gradual phasing out of psychiatric hospitals (PH) and the creation of comprehensive community-based systems. However, these changes have taken place at different times and in different forms. There are now three different organizational and care models operating in Italy: in the first, common in Southern Italy, the former PH and the new general hospital general wards (GHPW) coexist; in the second, outpatient departments complement the above facilities, but the hospital activity remains central; in the third model, a community model has been given priority-the so-called community priority. While many reports have been published describing the activity of some of the services adhering to the third model, no report has been published specifically describing the activity of services which work according to the second model, such as Cremona. In this paper, the activity of the Cremona psychiatric services is described, and the consequences of the reform law and the problems related to an hospital-based activity are emphasized.