How does Chinese society define the class and stratum? Why do the classified methods and the standards of the class and stratum take place? The thesis primarily concentrates on studying the class and stratum in Chinese society. Reviewing class and stratification concepts, the reexamination of theories and the establishment of analytical framework, the thesis claims that the classified methods of the class and stratum are usually motivated by political purposes. That is to say, new class and the stratum categories derive from the alternations of political purposes. Hence, in addition to assisting readers to understand how Chinese class and stratum are classified, the result of the research can also predict the future development of class and stratum in Chinese society by means of the reformation of politics, economy, and the society.

Philosophiae Doctor - PhD / Histological observations revealed that oral epithelium originated from a single ectodermal layer. As the ectoderm grew so it differentiated into squamous epithelium. The first features of squamous differentiation were noticed at 8 weeks in utero in areas where keratinized mucosae were developing, and these were the changing of cuboidal to cylindrical basal cells and the subsequent growth of prickle cells from these cylindrical basal cells. The prickle cells merged with the existing primitive cells and at no stage could a separate squamous epithelial layer I such as the stratum tritermedium of the epidermis I be observed inside the mouth. At 12 weeks in utero squamous differentiation had reached a stage where acidophilic layers appeared in certain regions on the epithelial layer. The time of appearance of these layers varied from case to case. At this stage most of the primitive characteristics had disappeared from the keratinizing epithelium. Unlike the periderm of the skin which was shed into the amniotic fluid, shedding of primitive epithelial cells from the keratinizing squamous epithelium was not noticeable. Thence, the growth of keratinizing epithelium was followed by an increase of acidophilic layers, the appearance of keratohyaline granules in cells and, in some instances, full keratinization. The latter I however I was almost exclusively confined to the vermilion border of the lip. The squamous epithelium of the lining mucosa, which is unkeratinized I developed at a much slower tempo. It retained its cuboidal-shaped basal cells and the primitive features of the overlying cells were lost only at about 4- 5 months in utero I when squamous differentiation set in. At no stage was the squamous differentiation a prominent feature. At junctions between keratinized and unkeratinized epithelia and epidermis the epithelium exhibited features of both types of epithelia that were being joined. This was especially noticeable at the junction between vermilion epithelium and epidermis, where part of the vermilion epithelium displayed a prominent intermediate type of layer. Similarly, acidophilic layers of keratinizing epithelium merged imperceptibly with the walls of cells of unkeratinizing epithelium, creating a small region of an unkeratinizing type of epithelium with keratinized cells. Thus the development of the oral epithelium is through differentiation and renewal of epithelial cells: the ectodermal layer developes into an epithelial layer which is recognised by its squamous appearance. The subsequent growth is by constant renewal of this differentiated epithelium. The pattern of epithelial development I the appearance of the junctional epithelia and the manner in which acidophilic layers merge with unkeratinized epithelial cells I indicate a unity between these epithelia. According to these developmental features, the epithelium of the mouth and epidermis can be classified into less differentiated and better differentiated, but with a commonbackground for these epithelia. When the formation and the established appearance of keratin in the mouth and on the skin was compared histologically I ultrastructurally and histochemically I a unity between these features became apparent. Ultrastructurally it appeared that keratin consisted basically of 2 cytoplasmic constituents: tonofilaments and a fine granular substance. The tonofilaments were gathered at first into bundles and then broken up into finer tonofibrils. These finer fibrils mixed with a granular ground substance to form a homogenous granular filamentous material. This product can be regarded as a pre-keratin. With the addition of a keratohyaline layer to the process I keratin was formed, Apart from the keratohyaline granules several additional changes took place in cells concerned in this process I whether keratin was formed or not. These changes were flattening of cells, extensive interdigitation between cell walls, disappearance of micro-villi I loss of structure in desmosomes I thickening of cell walls and the disappearance of glycogen from cells. Some of these features were displayed in each of the types of epithelium examined here.

The transdermal delivery of drugs has a lot of advantages above other routes of delivery, such as the avoidance of first-pass hepatic and intestinal metabolism, the non-invasive infusion of drugs, etc. However, the transdermal delivery of drugs, especially hydrophilic drugs, is limited due to the lipophilic nature of the stratum corneum. Methotrexate is a folic acid antagonist with antineoplastic activity and is used for the treatment of psoriasis and Kaposi's sarcoma. The permeation of methotrexate through the skin for systemic use is however limited due to its high molecular weight, the fact that it is mainty dissociated at physiological pH and its hydrophilic nature (Alvarez-Figueroa et al.. 2001). Thus the aim of my study was to enhance the permeation of methotrexate with the use of terpene. Terpenes are lipophilic in nature and have Log P values of around 2-4 (Godwin & Michniak, 1999). These characteristics make them excellent candidates as penetration enhancers. Terpenes are not only used for penetration enhancers, but in a huge number of other products, such as aromatherapeutic oils. For this reason the permeation of the terpenes through human skin and the effect of methotrexate on this permeation were also determined. The following enhancers were used in this study: menthol, menthone. isomenthol, limonene, B-myrcene, a-pinene and 1,8-cineole Five different sets of experiments were done in this study: a) a control experiment with methotrexate in the absence of the terpenes without ethanol; b) a control experiment with methotrexate in the absence of the terpenes with ethanol: c) experiments with methotrexate in the presence of the terpenes; d) control experiments with the terpenes in the absence of methotrexate and e) experiments with tile terpenes in the presence of methotrexate. For this study only human female abdominal skin was used. A saturated solution of methotrexate in water:propylene glycol (50:50) with a pH between 4 and 5 (Vaidyanathan et al., 1985) was used as the model drug and the receptor phase was PBS-buffer (pH=74) and water:ethanol (50:50) for HPLC and GC analysis respectively. The dilfusion apparatus used consisted of Vertical Franz diffusion cells with a capacity of 2 ml and a diffusion area of 1.075 cm2. The cells were placed in a water bath (+- 37 "C) on magnetic stirrers for the duration of the experiment. After the receptor phase was placed in the receptor compartment the cells were equilibrated for an hour before putting 25 ul of a 5% terpene solution in absolute ethanol on the skin in the donor compartment. This was left for half and hour to allow evaporation of the ethanol. The saturated solution of the methotrexate was now placed on the skin in the donor compartment. The experiments for methotrexate stretched over a period of 12 hours and samples were collected every 2 hours. The terpene experiments were performed over a 24-hour period and samples were taken at 2,4,6,12 and 24 hours. The concentration methotrexate permeated was determined by using HPLC-analysis and terpenes by using GC-analysis. The flux (ug/cm2/h), kp(cm/h), lag time (h) and enhancement ratio were calculated to compare the methotrexate permeation in the control and actual experiments. The results showed that a-pinene, B-myrcene and isomenthol enhanced the permeation of methotrexate most, although all the terpenes had an enhancing effect. They produced a 4- fold increase in the flux values of methotrexate. Due to the fact that the terpene experiments were only a semi-quantitative evaluation only the percentage terpenes that permeated was calculated. The experiments were done on all the terpenes except apinene. All the terpenes permeated the skin with menthol having the highest permeation. The results also showed that methotrexate did have an effect on the terpene permeation. Menthone and menthol's permeation was higher in the presence of methotrexate, while the other terpenes had a higher permeation in the absence of methotrexate. The reason for this is not clear. In conclusion, the study revealed that the enhancers used did have an enhancing effect on methotrexate permeation. This could be due to the extraction or disruption of lipids by the terpenes (Zhoa & Singh, 2000) or an increase in diffusivity and partitioning. The terpene experiments also showed that the terpenes do permeate the skin and that methotrexate does have an effect on this permeation. / Thesis (M.Sc.)--North-West University, Potchefstroom Campus, 2004.

Kallikrein-8 (KLK8) is a relatively-uncharacterized epidermal protease. Although proposed to regulate wound-healing and barrier repair in KLK8-deficient mouse skin, KLK8-catalytic activity was never demonstrated in human epidermis and its regulators and targets remain largely unknown. KLK8 overexpression was reported in inflammatory skin diseases, but the underlying mechanisms are poorly understood. In this thesis, we elucidated for the first time KLK8-specific activity in normal human non-palmoplantar stratum corneum and sweat, and identified epidermal regulators and targets that augment its involvement in a skin-barrier proteolytic cascade. Given that inflammatory skin diseases have interlinked immune and epidermal roots, we hypothesized that epidermal KLK8 expression is distinctly regulated by the aberrant T-cell immunity implicated in the two common skin diseases, psoriasis and atopic dermatitis, independent of skin-barrier insults. We profiled secretion of KLK8 by normal human keratinocytes post-treatment with T-helper (Th1, Th17 and Th2) cell-derived cytokines, and investigated the effect of KLK8 overexpression on terminal keratinocyte differentiation and innate immunity gene expression. Our results show that TNFα and IL-17A synergistically induce potent KLK8 hyper-secretion, while IL4 and IL13 reduce its expression. TNFα and IL-17A overexpression and KLK8 hyperactivity resulted in hyperkeratosis and upregulation of keratinocyte innate defense genes’ expression mimicking psoriatic lesions. Consistently, KLK8 expression was reduced in lesional skin of atopic dermatitis patients and significantly elevated in lesional skin and sera of psoriatic patients. KLK8 levels correlated with psoriasis skin severity and were significantly reduced by effective treatment with biologic TNFα-blockers, correlating positively with psoriasis clearance. Thus, KLK8 is a new epidermal psoriasis therapeutic target. We performed high throughput screens of small molecule compound libraries to identify KLK8-specific inhibitors and discovered promising KLK8 small molecule inhibitors with IC50s in the nanomolar range. This thesis provides original findings corroborating KLK8 as an active serine protease in normal human skin and a down-stream epidermal respondent to TNFα and IL17A overexpression in psoriatic skin. Our novel KLK8-specific inhibitors may have future potential as topical barrier-enhancing agents in psoriasis.

The transdermal delivery of drugs has a lot of advantages above other routes of delivery, such as the avoidance of first-pass hepatic and intestinal metabolism, the non-invasive infusion of drugs, etc. However, the transdermal delivery of drugs, especially hydrophilic drugs, is limited due to the lipophilic nature of the stratum corneum. Methotrexate is a folic acid antagonist with antineoplastic activity and is used for the treatment of psoriasis and Kaposi's sarcoma. The permeation of methotrexate through the skin for systemic use is however limited due to its high molecular weight, the fact that it is mainty dissociated at physiological pH and its hydrophilic nature (Alvarez-Figueroa et al.. 2001). Thus the aim of my study was to enhance the permeation of methotrexate with the use of terpene. Terpenes are lipophilic in nature and have Log P values of around 2-4 (Godwin & Michniak, 1999). These characteristics make them excellent candidates as penetration enhancers. Terpenes are not only used for penetration enhancers, but in a huge number of other products, such as aromatherapeutic oils. For this reason the permeation of the terpenes through human skin and the effect of methotrexate on this permeation were also determined. The following enhancers were used in this study: menthol, menthone. isomenthol, limonene, B-myrcene, a-pinene and 1,8-cineole Five different sets of experiments were done in this study: a) a control experiment with methotrexate in the absence of the terpenes without ethanol; b) a control experiment with methotrexate in the absence of the terpenes with ethanol: c) experiments with methotrexate in the presence of the terpenes; d) control experiments with the terpenes in the absence of methotrexate and e) experiments with tile terpenes in the presence of methotrexate. For this study only human female abdominal skin was used. A saturated solution of methotrexate in water:propylene glycol (50:50) with a pH between 4 and 5 (Vaidyanathan et al., 1985) was used as the model drug and the receptor phase was PBS-buffer (pH=74) and water:ethanol (50:50) for HPLC and GC analysis respectively. The dilfusion apparatus used consisted of Vertical Franz diffusion cells with a capacity of 2 ml and a diffusion area of 1.075 cm2. The cells were placed in a water bath (+- 37 "C) on magnetic stirrers for the duration of the experiment. After the receptor phase was placed in the receptor compartment the cells were equilibrated for an hour before putting 25 ul of a 5% terpene solution in absolute ethanol on the skin in the donor compartment. This was left for half and hour to allow evaporation of the ethanol. The saturated solution of the methotrexate was now placed on the skin in the donor compartment. The experiments for methotrexate stretched over a period of 12 hours and samples were collected every 2 hours. The terpene experiments were performed over a 24-hour period and samples were taken at 2,4,6,12 and 24 hours. The concentration methotrexate permeated was determined by using HPLC-analysis and terpenes by using GC-analysis. The flux (ug/cm2/h), kp(cm/h), lag time (h) and enhancement ratio were calculated to compare the methotrexate permeation in the control and actual experiments. The results showed that a-pinene, B-myrcene and isomenthol enhanced the permeation of methotrexate most, although all the terpenes had an enhancing effect. They produced a 4- fold increase in the flux values of methotrexate. Due to the fact that the terpene experiments were only a semi-quantitative evaluation only the percentage terpenes that permeated was calculated. The experiments were done on all the terpenes except apinene. All the terpenes permeated the skin with menthol having the highest permeation. The results also showed that methotrexate did have an effect on the terpene permeation. Menthone and menthol's permeation was higher in the presence of methotrexate, while the other terpenes had a higher permeation in the absence of methotrexate. The reason for this is not clear. In conclusion, the study revealed that the enhancers used did have an enhancing effect on methotrexate permeation. This could be due to the extraction or disruption of lipids by the terpenes (Zhoa & Singh, 2000) or an increase in diffusivity and partitioning. The terpene experiments also showed that the terpenes do permeate the skin and that methotrexate does have an effect on this permeation. / Thesis (M.Sc.)--North-West University, Potchefstroom Campus, 2004.

No description available.

The purpose of this study was to determine the effect of stratum corneum (SC) hydration by distilled water on SC ion content and sweat ion concentrations as measured by occlusive sweat patch. 10 men and 10 women completed approximately 40 minutes of moderate exercise in the heat. Select skin sites were hydrated before sweating by adhering cylinders of distilled water to forearm skin. SC samples were taken before and after exercise using the tape stripping (TS) method and sweat samples were taken with homemade filter paper sweat patches with a tegaderm backing. An increase in SC hydration was verified by a reduction in SC potassium concentration (p<0.05). SC hydration caused a significant decrease in sweat potassium (K+), calcium (Ca++), and lactate (Lac-) concentration: K+ =8.14 ± 0.46 to 6.56 ± 0.46, Ca++ = 0.86 ± 0.17 to 0.67 ± 0.18, Lac- = 11.64 ± 1.36 to 8.82 ± 1.11, euhydrated to hyperhydrated respectively(p<0.05). SC sodium (Na+) and K+ concentration increased after sweating without a sweat patch (p<0.05). Our data do not dispute the idea that electrolytes can be leached from the SC by distilled water or sweat trapped within an occlusive dressing. However, our data indicate that during normal sweating the SC "dehydrates" resulting in an increase in the electrolyte concentration. As such, we propose that the occlusive dressing does trap sweat on the skin but the important end result is that it prevents water movement out of the SC and thereby producing a more concentrated sweat.

The skin is an amazingly resilient and relatively impermeable barrier that provides protective, perceptive and communication functions to the body (Ramachandran & Fleisher, 2000). The stratum corneum is widely accepted as the barrier of the skin - limiting the transport of molecules into and across the skin. One of the bottlenecks in the successful development of transdermal drug delivery devices is the fact that the skin (more accurately, the stratum corneum - SC) tends to control the rate of drug transport. This makes it very difficult to influence or regulate the transdermal drug absorption kinetics from outside, Le. by means of the vehicle. A possible, and even elegant, solution may be the use of so-called "penetration enhancers", thereby suppressing the dominant role of the stratum corneum penetration barrier (Bodde et al., 1990). For this study 5-fluorouracil (5-FU), a polar hydrophilic drug, was chosen as model drug to study its penetration through the stratum corneum. Terpenes used as possible penetration enhancers for 5-FU were menthol, isomenthol, menthone, l3-myrcene, limonene and 1,8-cineole. In previous studies, terpenes with low skin irritancy and low systemic toxicity, were found to be effective penetration enhancers for a number of hydrophilic and lipophillic drugs (Cornwell & Barry, 1994; Cornwell et a/., 1996; Godwin & Michniak, 1999). The objective of this study was to determine the different flux rates of 5-FU in the absence of any pre-treatment of the stratum corneum and also through ethanol and selected terpene pre-treated SC. The effect of each terpene on the penetration of 5-FU was determined. The penetration of the selected terpenes themselves through the human stratum corneum was also determined in vitro permeation studies were performed using vertical Franz diffusion cells with human skin (stratum corneum). A saturated aqueous solution of 5-fluorouracil in the absence and presence of pre-treatment of the SC was used as the donor phase. Pre-treatment was performed by applying a 5 % terpene solution or absolute ethanol to the SC half an hour before the saturated III solution was applied in the donor compartment. A 50/50 ethanol/water solution was used as the receptor phase. All the experiments were conducted over a 24 h period. The 37°C temperature was held constant by means of a water bath. For the analysis of 5-FU flux rates, samples from the receptor compartment were obtained and were analysed by means of high-pressure liquid chromatography (HPLC). In order to determine the cumulative percentage of terpenes penetrated through human stratum corneum, the samples were analysed by gas chromatography (GC). In this study, only menthol and isomenthol (both oxygen-containing terpenes) showed a statistically significant increase on the flux of 5-FU, with flux values of 1.13 +- 0.38 and 1.45 +- 0.68 ug/cm2/h, respectively, compared to untreated skin with a flux value of 0.54 +- 0.23 ug/cm2/h for 5-FU. It was also proved that ethanol itself had an enhancing effect on 5-FU and showed synergistic effects on the enhancement activities of all the terpenes. It was found that all the terpenes (applied as a 5 % solution in ethanol) penetrated through the stratum corneum in the absence of 5-fluorouracil. 5-Fluorouracil had either an increasing or decreasing effect on the penetration of the terpenes. From these findings, it could be concluded that oxygen-containing terpenes had the best penetration enhancing effect on 5-FU and that menthol and isomenthol were the most effective penetration enhancers, although the extend of penetration enhancement is not large enough for clinical application. All the terpenes have the ability to penetrate through human stratum corneum, and 5-FU either had an increasing or decreasing effect on their penetration. / Thesis (M.Sc.)--North-West University, Potchefstroom Campus, 2004.

The skin is the largest and most easily accessible organ of the human body thus making it the ideal route for systemic drug delivery. The transdermal route of drug delivery offers several advantages compared to the traditional routes including elimination of first pass metabolism and higher patient compliance. However, many drugs are topically and systemically ineffective when applied onto the skin, due to their almost complete failure to penetrate the skin. The main limitation lies in the stratum corneum, the barrier of the skin, which prevent the drug from reaching the deeper skin strata. 5-Fluorouracil is a polar hydrophilic drug and is therefore not a good penetrant through skin. A popular technique to increase transdermal permeation is to use a penetration enhancer, which reversibly reduce the permeability barrier of the stratum corneum. The primary aim of this study was to determine the effect of Brij 97 in the presence and absence of carrageenan on the transdermal delivery of 5-fluorouracil. The formulations were identified by means of confocal laser scanning microscopy and measurement of the particle size. The zeta-potential was measured to determine whether the formulations were stable and the pH was measured to determine if the internal structures of the formulations were affected by the drug. The drug released from the formulations was measured with a VanKel dissolution apparatus. In vitro transdermal diffusion studies were performed using vertical Franz diffusion cells with human epidermal skin. Histopathological studies were carried out on human epidermis skin to determine if the surfactant, Brij 97, had any effect on the skin. Through confocal laser scanning microscopy and particle size measurements, the 4 and 8% Brij 97 formulations without carrageenan could be identified as emulsions while the 15 and 25% Brij 97 formulations without carrageenan could be identified as microemulsions. The 4, 8, 15 and 25% Brij 97 formulations containing carrageenan could be identified as gels. The results obtained from the zeta-potential analysis indicated that the 4 and 8% Brij 97 formulations without carrageenan and 4% Brij 97 formulation with carrageenan are the most electronegative and thus the most stable. The pH measurements confirmed that the internal structure of the formulations was not influenced by the drug. 5-Fluorouracil was released from the formulations. The 4 and 8% Brij 97 formulations without carrageenan had an enhancing effect on the penetration of 5-fluorouracil while the 4, 8, 15 and 25% Brij 97 formulations with carrageenan and the 15 and 25% Brij 97 formulations without carrageenan had an hindering effect on the penetration of 5-fluorouracil. Although carrageenan led to good adhesiveness of the formulation on the skin, it did not lead to the enhancement of the penetration of 5-fluorouracil through the skin. When histopathological studies were carried out on female human abdominal skin, Brij 97, the surfactant, was found to have no damaging effect on the skin structure. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2006.

The skin is an amazingly resilient and relatively impermeable barrier that provides protective, perceptive and communication functions to the body (Ramachandran & Fleisher, 2000). The stratum corneum is widely accepted as the barrier of the skin - limiting the transport of molecules into and across the skin. One of the bottlenecks in the successful development of transdermal drug delivery devices is the fact that the skin (more accurately, the stratum corneum - SC) tends to control the rate of drug transport. This makes it very difficult to influence or regulate the transdermal drug absorption kinetics from outside, Le. by means of the vehicle. A possible, and even elegant, solution may be the use of so-called "penetration enhancers", thereby suppressing the dominant role of the stratum corneum penetration barrier (Bodde et al., 1990). For this study 5-fluorouracil (5-FU), a polar hydrophilic drug, was chosen as model drug to study its penetration through the stratum corneum. Terpenes used as possible penetration enhancers for 5-FU were menthol, isomenthol, menthone, l3-myrcene, limonene and 1,8-cineole. In previous studies, terpenes with low skin irritancy and low systemic toxicity, were found to be effective penetration enhancers for a number of hydrophilic and lipophillic drugs (Cornwell & Barry, 1994; Cornwell et a/., 1996; Godwin & Michniak, 1999). The objective of this study was to determine the different flux rates of 5-FU in the absence of any pre-treatment of the stratum corneum and also through ethanol and selected terpene pre-treated SC. The effect of each terpene on the penetration of 5-FU was determined. The penetration of the selected terpenes themselves through the human stratum corneum was also determined in vitro permeation studies were performed using vertical Franz diffusion cells with human skin (stratum corneum). A saturated aqueous solution of 5-fluorouracil in the absence and presence of pre-treatment of the SC was used as the donor phase. Pre-treatment was performed by applying a 5 % terpene solution or absolute ethanol to the SC half an hour before the saturated III solution was applied in the donor compartment. A 50/50 ethanol/water solution was used as the receptor phase. All the experiments were conducted over a 24 h period. The 37°C temperature was held constant by means of a water bath. For the analysis of 5-FU flux rates, samples from the receptor compartment were obtained and were analysed by means of high-pressure liquid chromatography (HPLC). In order to determine the cumulative percentage of terpenes penetrated through human stratum corneum, the samples were analysed by gas chromatography (GC). In this study, only menthol and isomenthol (both oxygen-containing terpenes) showed a statistically significant increase on the flux of 5-FU, with flux values of 1.13 +- 0.38 and 1.45 +- 0.68 ug/cm2/h, respectively, compared to untreated skin with a flux value of 0.54 +- 0.23 ug/cm2/h for 5-FU. It was also proved that ethanol itself had an enhancing effect on 5-FU and showed synergistic effects on the enhancement activities of all the terpenes. It was found that all the terpenes (applied as a 5 % solution in ethanol) penetrated through the stratum corneum in the absence of 5-fluorouracil. 5-Fluorouracil had either an increasing or decreasing effect on the penetration of the terpenes. From these findings, it could be concluded that oxygen-containing terpenes had the best penetration enhancing effect on 5-FU and that menthol and isomenthol were the most effective penetration enhancers, although the extend of penetration enhancement is not large enough for clinical application. All the terpenes have the ability to penetrate through human stratum corneum, and 5-FU either had an increasing or decreasing effect on their penetration. / Thesis (M.Sc.)--North-West University, Potchefstroom Campus, 2004.