Mucoadhesive polymers as efficient drug delivery systems

The drug action can be reinforced as a result of the development of new drug delivery systems. Over the past few decades, mucosa/ drug delivery has received a great deal of attention to improve both the local and systemic drug effects. Drug delivery across the mucosa bypasses the first-pass hepatic metabolism and avoids the degradation caused by the gastrointestinal enzymes. Mucoadhesive dosage forms are designed to enable prolonged retention at the desirable site of action, provide sustained release of drug and thus, lead to an improved bioavailability, as well as therapeutic outcomes. Compared with other mucosa/ rissues, vaginal mucosa/ cavity is more appropriate and attractive for drug delivery. In addition, a prolonged contact of mucoadhesive dosage forms with the vaginal mucosa may be achieved more easily than at other absorption sites like rectum or intestinal mucosa. This review aims to highlight the recent advances in the study of mucoadhesion and mucoadhesive polymers. It provides an overview of the structure of mucosa/ membranes, the mechanism and theories involved in mucoadhesion, and finally it describes briefly the main characteristics and the advantages of vaginal mucoadhesive drug delivery systems compared with other delivery systems

Functional change of dextran-modified alpha-amylase from bacillus acidocaldarius

ALPHA-AMYLASE from Bacillus acidocaldarius was modified by covalent coupling to activated dextran with retained activity of 77.7%. After conjugation, the enzyme was stable within a broader pH range than the native enzyme and its optimum temperature increased by 10°C compared to the native enzyme. The conjugated a amylase exhibited a higher K[m] [Michaelis constant], lower V[max] [maximal reaction rate] and lower E[A] [activation energy] than the native enzyme. Covalent attachment of alpha- amylase to activated dextran protected the enzyme against heat inactivation. In the presence of the substrate, the conjugated enzyme retained 68.2% of its original activity after incubation at 70°C for 30 min which was more than that retained by the native enzyme [50.3%] under the same conditions. The calculated t[1/2] [half-life time] values of heat inactivation energy at 50, 60°C were 89 and 56 mm, respectively for the conjugated enzyme, whereas at these temperatures the native enzyme was less stable [t[1/2] 60 and 47 min, respectively]. The deactivation rate constant at 80°C for the conjugated a-amylase is about 11.9x10[-3]/ min, which is lower than that of the native enzyme [14.8x10[-3]/ min]. Conjugated a-amylase was more stable against chemical denaturation than the native enzyme, and retained 70.6% of its activity in presence of CuSO[4] [10 mM] while the native form of retained only 34.1%

Enhancement of solubility and dissolution of nimesulide using solubilization, solid dispersion and complexation techniques

Nimesulide is a preferential COX-2 inhibitor. It has high anti-inflammatory, antipyretic and analgesic activities. It has poor aqueous solubility [0.01mg/ml]. Solubility of nimesulide was studied using different cosolveni mixtures and various classes of nonionic surfactants. Dimethylacetamide [DMA,]; at 10% v/v exhibited the highest solubilizing effect [10-fold] towards nimesulide as compared with other cosolvents. Among the tested nonionic surfactants at 10% W/V, brij 58 which exhibited the highest solubilization effect [39-fold]. The dissolution of nimesulide from solid dispersions was also studied Solid inclusion complexes of nimesulide with beta-cyclodextrin [beta-CD] and hydroxypropyl beta-cyclodextrin [HP beta-CD] were prepared at a molar ratio of 1:1. Eutectic mixtures were obtained at weight ratio of 1:9 binary systems as confirmed by DSC studies. The dissolution studies indicated that the highest relative amounts dissolved were obtained from solid dispersions as compared with physical mixtures or pure nimesulide. Also higher relative amounts dissolved were obtained with polyvinylpyrrolidones [PVPs] at weight ratio of nimesulide/PVP 40000 1.7. Physicochemical characterization of pure drug, PVP 40000, nimesulide/PVP 40000 solid dispersion and the physical mixture at this ratio were conducted by DSC, FTIR, X-RPD and SEM. The DSC thermograms and X-RPD patterns demonstrated that nimesulide existed in an amorphous form and there is an intermolecular hydrogen bond between the drug and the carrier as shown from FTIR analysis. SEM images confirmed the absence of the crystalline structure of nimesulide in the solid dispersion

Development and evaluation of nefopam hydrochloride microcapsules

An attempt was performed to encapsulate Nefopam hydrochloride, a highly water soluble drug, by a modified emulsion solvent evaporation / extraction technique, using cellulose acetate butyrate [CAB] as a coating polymer. The influence of core/coat ratio [1:2, 1:1 and 2:1 ratio] on the yield, drug loading, size distribution as well as the release characteristics and surface topography of the prepared microcapsules was investigated. The obtained microcapsules exhibited higher encapsulation efficiency and a decreased release rate in simulated gastric fluid [S.G.F. pH 1.2] and simulated intestinal fluid [S.I.F. pH 7.4]. On the other hand, the entrapment efficiencies increased [from 104.66 to 141.26, core coat ratio 1:1] and the release rate decreased with increasing microcapsule size [from 250 to 512.5 micro m] and/or theoretical drug loading of microcapsules. Kinetic assessment of the release rate of microcapsules using different mathematical models has shown that the release followed Ritger-Peppas diffusion release kinetics

Effect of therapeutic electrical stimulation on spasticity, gait pattern and ankle range of motion in spastic cerebral palsied children

This study aimed to evaluate the effect of therapeutic electrical stimulation [TES] of the anterior tibial group of muscles on spasticity, range of motion [ROM] of the ankle joint and gait patterns in children with spastic CP. The study was carried out at neurology outpatient clink of Alexandria University Children's Hospital [El-Shatby]. Sixty spastic cerebral palsied children were randomly selected. They were divided into three groups I, II, and III. Group [I] comprised 34 children with spastic hemiplegia. Group [II] comprised 19 children with spastic diplegia. Group [III] comprised 7 children with spastic quadriplegia. Patients of the three groups were treated by electrical stimulation of the anterior tibial group of muscles at a frequency of 30 Hz with pulse width of 100ns for 7 seconds contraction and 15 seconds relaxation for one hour every other day for 3 months. Re-assessment was done using the following parameters: self-concept assessment, spasticity assessment of the ankle joint, goniometry of the ankle joint and gait pattern assessment [step length and step width] was done at the end of the study period. The study showed that TES had a significant positive effect on spasticity reduction in all types of spastic CP. Also, TES had a significant positive effect on ankle joint angle where it increased the passive ROM in all types of spastic CP. Furthermore, TES had a significant positive effect on gait patterns in the form of an increase in step length and decrease in step width in all types of spastic CP. Also, it had a significant positive effect on self-concept score in all types of spastic CP. Therapeutic electrical stimulation [TES] of the anterior tibial group of muscles in children with spastic cerebral palsy is an effective modality in decreasing spasticity of the extensor group of muscles of lower limb and increasing ability of dorsiflexion of the foot which will increase joint range of motion, improve gait patterns. All these will raise the patients' self concept with better quality of life despite cerebral palsy

Pathological and molecular studies on avian leukosis virus subgroup [J] in chicken parents flocks

The present study was carried out on 10 parent chickens flocks collected from different provinces. The examined cases were classified into 47 commercial layers and 198 broiler parents to study the gross and microscopical lesions of different tumors induced by avian leukosis subgroup-J [ALV-J] in broiler breeders and layers flocks. Serological tests were conducted on 245 serum samples to detect the antibodies of ALV-J. Polymerase chain reaction PCR was carried out on tissue samples to confirm the presence of DNA of ALV subgroup J. Myeloid leukosis was recorded in four broiler flocks induced by the novel sub group-J of ALV. Pathological findings of infected parent chickens flocks revealed multiple neoplastic nodules in different organs including liver, kidney, gonads, intestine, skeletal muscle and bone. Histologically, the main constituent of tumor lesions was mature and immature myelocytes. Nephroblastoma was considered as the first recorded cases in Egyptian broiler parent flocks affected with ALV subgroup J. The results of this work concluded that the histopathological examination plays a crucial and decisive role in diagnosing different types of neoplasm caused by avian leukosis virus subgroup-J. The application of PCR test verified the presence of DNA of ALV-J that induced the tumors of myeloid leukosis

Some topographical and morphological studies on air sacs of domestic pigeon [Columba livia domestica] using corrosion casts

The work was carried out on fifteen adult pigeons of both sexes. The gross morphological features of the air sacs were thoroughly investigated using Vinyl chloride acetate corrosion casts. It was found that the pigeon as an example of a powerful flying bird had 4 pairs of transparent air sacs [cervical, cranial thoracic, caudal thoracic and abdominal], in addition to an unpaired interclavicular sac. They were symmetrically occupying either side of the body cavity. The cervical sacs aerated the cervical vertebrae approximately from the 3rd or 4th as well as the first two thoracic vertebrae. The single interclavicular air sac was the most complicated among all air sacs in the pigeons. It occupied the ventral part of the thoracic inlet and overlay the cervical sacs laterally and connected with their cranial ends. Meanwhile, the interclavicular sac gave off extrathoracic humeral and axillary diverticula, which pneumatized the humeri and bones of the pectoral girdles. It was also observed that the cranial and caudal thoracic air sacs showed no bony communications, and never aerates bones. The paired abdominal sacs were larger than the other air sacs. They enclosed between their medial surfaces the intestinal tract, kidneys and the gonads. Also, each of them sent a diverticulum which ventilated the interior of the pelvic bone and the synsacrum. The obtained results of the air sacs in the pigeon were discussed with the findings given by previous authors in other species of birds

Evaluation of progress of labor using ultrasonographic measurement of uterine wall thickness

During labor, the uterus is transformed into two distinct segment. The active upper segment which becomes thick and the relatively passive lower segment which becomes thin with the progress of labor. The ratio between both segments used to indicate the progress of labor and imminent delivery. The safety of vaginal delivery depends mainly on the thickness of the lower uterine segment especially in patients with previous uterine scare or high risk pregnancy. Evaluation of progress of labor by measurement of the uterine wall thickness sonographyically to identify the safety of vaginal delivery in the our aim. 43 full term pregnant women early in labor mean age 24.93, DS 4.03 years, 10 primigravida and 33 multigravida [Parity < 3] vertex presention, with no risk factors or uterine scar. Repeted measurement of upper and lower uterine segments thickness sonographically were done in relation to cervical dilation which also measured. The result shows a statistically significant progressive increase in upper uterine segment wall thickness in relation to cervical dilatation and the lower uterine segment shows progressive thinning, the ratio was 1.05 in late pregnancy, 1.37 at the beginning of active phase of labor and 9.03 at full cervical dilator. We conclude that labor is imminent when the mean lower uterine segment thickness was < 0.35 cm and mean upper uterine segment thickness > 3.0 cm this should be considered in high risk pregnancies when digital examination carries the risk of ascending infection in cases of PROM or ante partum hemorrhage

use of doppler flow velocity wave form of uterine and umbilical arteries as a method of fetal surveillance during progress of labor

Doppler velocimetry is a noninvasive, inexpensive technique which has a place in obstetric practice through early detection of fetal compromise and reduction of fetal morbidity and mortality via proper intervention. 43 full term pregnant women early in labor 10 primigravid and 33 multigravid [Parity < 3] vertux presention, which no major risk factor or previous uterine scar and normal CT or at the beginning of labour. Mean age 24.93 Y, SD 4.03 years. Measurements of uterine and umbilical arteries wave from through labour in relation to cervical dilatation were done and RI, PI, S/D were calculated. Shows changes in the mean uterine and umbilical arteries flow velocity waveform indices [RI, PI and S/D ratio] during peak uterine contraction which shows a progressive increase in all indices as the cervical dilation progressed. The results were statistically significant as P value were 0.000 for all three indices. Assessment of uterine and umbilical arteries Doppler should be an integral part of routine examination of high risk patient during labor

Urinary fibronectin in bladder cancer: is it a reliable tumor marker?

Twenty eight patients with bladder cancer and 21 with different benign urological diseases were included. Healthy persons [15] were tested as a control group. A complete history, general and local examinations, routine investigations as well as urinary fibronectin assay were done using an ELISA technique. Radiodiagnostic studies and cystoscopic examination; and biopsy taking; were then performed. The marker showed a mean value of 260 microgm/L in cases of bladder cancer 96.19 microgm/L in benign urological diseases, and 88.5 microgm/L in control group. It had a 75% sensitivity, 58.8% specificity, and 86.4% overall accuracy.The marker has good diagnostic and fair prognostic abilities

Serum levels of soluble CD95 in patients with systemic lupus erythematosus

The present study was carried out on 30 patients with systemic lupus erythematosus [SLE] and ten apparently healthy individuals as a control group.Systemic lupus erythematosus activity index [SLEDAI] was applied to all patients. Anti-double stranded DNA antibodies [Anti-dsDNA Abs.], interleukin-18 [IL-18] and soluble CD95 [Apo-1/Fas] were determined in the sera of all studied subjects. The mean +/-SD SLEDAI in all patients was 15.25+/- 6.76 . The anti-dsDNA antibodies was positive in all studied patients [mean +/- SD 264.36 +/- 114.85 IU/ml]. Serum IL-18 showed significant elevation in SLE patients as compared to the control group [Mean +/-SD 246.13+/- 114.32I U/ml vs. 45.5 +/- 7.32 IU/ml; p < 0.001]. Serum Soluble CD95 [sCD95] showed significant increase in all SLE patients as compared to the control group [Mean+/-SD 648+/-116.96 pg/ml vs. 270+/-50.24 pg/ml; p < 0.001]. Serum sCD95 also showed significant rise in SLE patients with moderate activity as compared to those with mild activity [Mean +/- SD 629.16+/- 72.54 pg/ml vs. 535 +/-35.97 pg/ml; p<0.05]. The serum level of sCD95 in SLE cases with severe activity showed significant increase when compared to those with moderate activity [Mean+/-SD 797.5 +/- 41.66 pg/ml vs. 629.16 +/- 72.54 pg/ml; p <0.001]. Anti-dsDNA antibodies showed significant positive correlation with SLEDAI [r=0.772; p<0.01]. IL-18 also showed a significant positive correlation with the SLEDAI [r=0.670; p<0.01]. Soluble CD95 showed significant positive correlation with SLDAI [r=0.865; p<0.01], with anti-dsDNA antibodies [r=0.775; p<0.01] and with IL-18 [r =0.722; p<0.01]. From these results it was concluded that serum sCD95 is increased in patients with systemic lupus erythematosus and it is correlated with anti-dsDNA antibodies, with IL-18 and with the disease activity, so it can be useful marker of disease activity for proper management and follow up of SLE patients

Pattern of relapse in breast cancer cases

This retrospective study included 957 female breast cancer patients. A metastatic investigation work was completed for all cases and all of them proved to be metastatic. Patients with incomplete data were excluded. Local recurrence in the chest wall and the axillary lymph nodes were studied. The local recurrences were 8.48%. It was found that the incidence of local recurrence increased in the late stages of the disease which was statistically significant. Also, the number of positive lymph nodes proved to be one of the significant factors affecting the local recurrence. Distant metastasis occurred in 31% of the patients. The most common sites of metastasis were bones, lungs, liver, supra clavicular lymph nodes and the brain; while, T3 and T4 had the highest incidence of distant metastasis and the nodal status significantly affected the distant metastasis as the highest incidence was observed in N2 cases

Nephrotoxic effects of silica dust

The hypothesis of chronic nephropathy in association with silica exposure is supported by several epidemiologic studies. Our study investigates the adverse effects of silica exposure on the kidneys, in both silicotic and non-silicotic workers. The studied population included an exposed group [n=112], working as millers in the manufacture of bricks, and in underground mining, and a referent group [n=51] matched for age, sex and socioeconomic status. Our results revealed renal affection caused by silica exposure which was proved to occur earlier than chest manifestations of silicosis and that laminin levels serve as an early indicator of renal dysfunction. Also laminin levels show positive correlation with the duration of exposure

Electron microscopic study on the liver and kidney of albino rat after imipenem administration

Imipenem [Tienam] a recently introduced carbapenem beta lactam antibiotic was administered to albino rats for different periods at doses relevant to those used in human to study its effect on the ultras tructure of kidney and liver as well as the serum levels of creatinine, urea, SGOT. SGPT and alkaline phosphatase. The observed renal ultrastructural changes were dependent on the duration of drug administration and confined primarily to the proximal convoluted tubule cells Specific lysosomal alterations were detected in the form of myelin like figures [myeloid bodies] within their cavities. The most stricking hepatic changes were swelling of mitochondriae with distortion of their cristae. disruption of the rough endoplasmic reticulum and accumulation of large lipid droplets. The above mentioned changes were more prominent when the drug was administered for 15 days. Serum creatinine increased after 5 days, while SGOT increased after 10 days. After 15 days of the the drug administration, serum levels of creatinine, urea, SGOT, SGPT and alkaline phosphatase become elevated significantly These ultrastructural and biochemical changes indicated that imipenem may induce renal or hepatic dysfunction in human so it should be given with caution in patients with renal or hepatic impairment

study of the anti-inflammatory activity of Nigella sativa L. and thymoquinone in rats

The anti-inflammatory activity of the volatile oil [v.o.] of Nigella sativa L. seeds and its active principle thymoquinone has been examined using carrageenan-induced oedema in rat hind paws and cotton seed pellet granuloma in rats. Both the v.o. and thymoquinone were found to produce a significant dose-dependent anti-inflammatory effect as evidenced by the significant inhibition of oedema formation and reduction of the granuloma weight. The v.o. [0.66 ml and 1.55 ml/Kg, Lp.] inhibited rat hind paw oedema formation by 64.12% and 96.26%, while thymoquinone [0.5, 1.0, 5 mg/Kg, Lp.] caused a reduction of38.85%, 56.63% and 104.88%, respectively. Indomethacin [3 and 9 mg/Kg, Lp.] inhibited the oedema by 46.90% and 67.83%, respectively. In addition, the v.o. [0.33 ml and 0.66 ml/Kg, Lp.] inhibited granuloma formation by 17.64% and 46.86%, while thymoquinone [3 and 5 mg/Kg, i.p.] reduced granuloma weight by 13.04% and 48.09%. These effects were nearly comparable to indomethacin [3 mg/Kg, i.p.] which reduced granuloma weight by 34.37%. It was suggested that the anti-inflammatory activity of the v.o. of Nigella sativa seeds may be due to inhibiting the generation of eicosanoids and lipid peroxidation

Primary reconstruction of human bite wounds of the face

The human bites is the worst of all bites, and primary repair of human bite wounds was not favored in all patients. Primary reconstruction of 37 human bite wounds of the face without clinical infection has been carried out successfully third day post bite. It was considered that debridement of wound edges to eliminate the devitalized tissue is the key to success

Some trace elements in idiopathic nephrotic syndrome

This study was carried out on 24 children [10 males and 14 females] with idiopathic nephrotic syndrome, aged from 3 to 7 years, to evaluate some trace elements in these children. The results obtained were compared with those obtained from 15 normal healthy controls of the same age and sex. A significant decrease was observed in the serum copper, zinc and selenium, while there was a significant increase in serum magnesium, as compared to normal controls. Serum zinc, copper, and selenium had a significant positive correlation with serum albumin, while serum magnesium had insignificant negative correlation with serum albumin. Serum zinc, copper and selenium correlated negatively with 24 hours urine proteins, but serum magnesium correlated positively with 24 hours urine proteins. It is concluded that these trace elements may be used as diagnosticc and prognostic processes in patients with idiopathic nephrotic syndrome

Management of traumatic liver injuries

In this series 90 patients with liver injury with variable severity were studied; 50 retrospectively [1985-1990] were reviewed and 40 prospectively [1990-1995] were reviewed and 40 prospectively [1991-1995] were managed according to special protocol. Surgical intervention was performed in unstable patients and nonoperative treatment was used for those who were hemodynamically stable on admission. Increasing experience resulted in fewer indications for resection in the prospective group and the nonoperative management rate was 37%. The overall mortality rate was 13% [16% in the retrospective and 10% in the prospective group]

Effect of hepatosplenic schistosomiasis on the hypothalamic-Pituitary-adrenal axis

To test the hypothalamic pituitary adrenal axis in hepatosplenic schistosomiasis [HSS], 40 adult Egyptian males were selected. They were composed of 4 groups: Compensated HSS [G1], decompensated HSS [G2], HSS with bilateral gynecomastia [G3] and healthy controls [G4]. They were subjected to full clinical examination and routine laboratory tests in addition to the ACTH and cortisol levels in plasma before [basal level] and after insulin-induced hypoglycemia as a dynamic test. The basal level of plasma ACTH in patients with compensated HSS was found to be significantly lower than that of the control [P <0.05]. It was even lower in the controls and in HSS associated with gynecomastis [P <0.001]. After insulin induced hypoglycemia, the level of ACTH was found to be significantly low in G2 and G3 compared with the controls. The level after stimulation was higher than the basal level in all groups including the controls. On the other hand, the basal level of serum cortisol was significantly low in patients with gynecomastia only compared with the controls. While, after insulin induced hypoglycemia the levels were found to be significantly low in G1 and G3 [P <0.001]. No correlations were found between serum albumin, SGPT or alkaline phosphatase and ACTH or cortisol levels. These findings could have its own application when a patient with HSS should undergo a major surgery