Lymphatic transport of orally administered drugs

Several therapeutic molecules such as lipophilic drugs and peptides suffer from the problems of low oral bioavailability. Improvement of their bioavailability and simultaneous prevention of the oral degradation of the prone molecules appears to be a challenge. Lymphatic system, which is responsible for the maintenance of fluid balance, immunity and metastatic spread of cancers, is also found to play a major role in the oral absorption of lipids and lipophilic drugs from intestine. The specialized structure of gut associated lymphoid tissue can be utilized as a gateway for the delivery of particulate systems containing drugs. Even though a large gap has existed in the field of lymphatic drug delivery, the introduction of a large number of lipophilic drugs and peptides has brought a renewed interest of research in this area. In this review, the mechanisms of intestinal lymphatic drug transport, approaches taken for the delivery of macromolecules, lipophilic and peptide drugs, biochemical barriers involved in intestinal drug absorption, and animal models used in the studies of intestinal lymphatic drug transport has been discussed.     

Vanadium-contaminated perioperatively administered infusion solutions and drugs

Vanadium was determined in 51 solutions and drugs for intravenous administration and in 6 salt components of a multitrace element solution using electrothermal atomic absorption spectrometry. The highest V contaminations were found in albumin solutions showing values of more than 600 μg/L V. Two heparines contained 14.3 and 122 μg/L V, respectively. In the ultratrace element solution, 14.8 μg/L vanadium were determined. The most contaminated salt of this solution was Mn(II)-dl-aspartate (12.8 μg V/g). The concentrations of unbound V (V _f ) in the albumin solutions were between 0.31 and 299 μg/L. The manufacturing process is the reason for V contamination. The biological half-life of V administered intravenously by albumin solutions in man was about 125 h.     

Numerical taxonomy of Bacillus isolated from orally administered drugs

Numerical taxonomy procedures were used to study 118 strains of Bacillus isolated from non-sterile drugs prepared for oral administration. Similarities between pairs of strains were calculated by the simple matching coefficient of Sokal and Michener (S_SM). Each strain was tested for 60 unit characters and three clusters were defined. The strains in each cluster presented a similarity level of at least 60%. Cluster A comprised the strains identified as Bacillus cereus (S_SM= 93·13%), cluster B contained three subgroups corresponding to the species B. pumilus, B. subtilis and B. licheniformis (S_SM= 84·35%) and cluster C also included three subgroups that belonged to the species B. firmus, B. lentus and B. badius (S_SM= 80·14%). The most discriminating tests were selected to differentiate the clusters from the subgroups. The feature with the highest discriminating power between clusters A and B was the lack of acid production from arabinose and mannitol. The Voges-Proskauer, methyl red tests and sensitivity to polymyxin B clearly distinguished cluster A from C. The Voges-Proskauer test and acid production from arabinose were the best to differentiate between B and C. Bacillus pumilus and B. subtilis differed in starch hydrolysis and B. licheniformis in growing anaerobically. To discriminate B. firmus from B. lentus the most important tests were the acid production from glucose and sucrose; intermediate strains were found. Bacillus badius was differentiated from B. firmus by 10 tests, and from B. lentus by the production of urease.     

Numerical taxonomy of Bacillus isolated from orally administered drugs

Numerical taxonomy procedures were used to study 118 strains of Bacillus isolated from non-sterile drugs prepared for oral administration. Similarities between pairs of strains were calculated by the simple matching coefficient of Sokal and Michener (SSM). Each strain was tested for 60 unit characters and three clusters were defined. The strains in each cluster presented a similarity level of at least 60%. Cluster A comprised the strains identified as Bacillus cereus (SSM = 93.13%), cluster B contained three subgroups corresponding to the species B. pumilus, B. subtilis and B. licheniformis (SSM = 84.35%) and cluster C also included three subgroups that belonged to the species B. firmus, B. lentus and B. badius (SSM = 80.14%). The most discriminating tests were selected to differentiate the clusters from the subgroups. The feature with the highest discriminating power between clusters A and B was the lack of acid production from arabinose and mannitol. The Voges-Proskauer, methyl red tests and sensitivity to polymyxin B clearly distinguished cluster A from C. The Voges-Proskauer test and acid production from arabinose were the best to differentiate between B and C. Bacillus pumilus and B. subtilis differed in starch hydrolysis and B. licheniformis in growing anaerobically. To discriminate B. firmus from B. lentus the most important tests were the acid production from glucose and sucrose; intermediate strains were found. Bacillus badius was differentiated from B. firmus by 10 tests, and from B. lentus by the production of urease.     

Absorption of experimentally administered materials by the hepatopancreas cells of the crayfish, Procambarus clarki

After long term starvation, the crayfish, Procambarus clarki was administered protein silver, iron lactate and olive oil, and its hepatopancreas was subsequently examined by electron microscopy. The reserve cells showed changes suggesting the absorption of these materials from the acinar lumen had taken place. In contrast, the hindgut of crayfish seemed to have no absorptive ability. In crustaceans the hepatopancreas is the largest gland in the body. The chief functions of this gland are the secretion of digestive juice into the stomach and absorption of digested food. It is also where materials which are necessary for hardening of animals that have undergone ecdysis are stored. Although these roles are commonly accepted, the absorptive ability of the gland has been rarely studied. Yonge (1924) and van Weel (1955) attempted to obtain evidence for the absorptive function of hepatopancreas cells of Nephrops norvegicus and Atya spinides using iron lactate and iron saccharate, and obtained some positive results. They used the histochemical Prussian blue test to demonstrate absorbed iron. Vonk (1960) referred to the results of a few authors who had tried to show fat deposits in reserve cells of the hepatopancreas after the administration of olive oil to the animals. But because starvation did not affect the quantity of stored fat in the hepatopancreas cells, the attempt failed to reveal the absorption of fat by the hepatopancreas. In the present paper, the authors describe the results of studies on the absorption of experimentally administered materials by hepatopancreas cells of the crayfish, Procambarus clarki, using electron microscopy.     

Stereospecificity of intraventricularly administered acetylmethylcholine antinociception.

We have previously reported that the intraventricular injection of acetylcholine increases latency in the mouse tail-flick test, the ED50 being 7.3 ug (1). This effect was reversed by five narcotic-antagonist analgesics in the same order of potency in which they antagonized morphine, and was found to be due to muscarinic receptor stimulation. It was also pointed out at that time that the intraventricular injection of acetylcholine would block the writhing response to intraperitoneally administered p-phenyl-quinone. In this preliminary communication, we present our results of the effect of the intraventricular injection of acetyl-choline on writhing induced by intraperitoneally administered acetylcholine. In addition, we present results of our studies in which we demonstrated stereospecificity of intravetricularly administered ministered acetylmethylcholines in causing antinociception.