**5. Conclusion**

*Pharmaceutical Formulation Design - Recent Practices*

prolonged the cell-killing effect of DOX.

delivery of therapeutics [77–79].

strated pH-sensitive drug release behavior.

while minimizing its systemic toxicity. The resulting microgels exhibited sensitivity to the pH and ionic strength of the surrounding environment and demonstrated that DOX was efficiently loaded into the microgels and released in a controlled fashion via an ion exchange mechanism. The antitumor activity of the released DOX was assessed using a human chordoma cell line revealed that OPF-SMA microgels

Tripahi et al. [74] developed a pH-sensitive intragastric floating polymer micro-

gel beads containing clarithromycin for the treatment of peptic ulcer. The optimized formulation successfully maintained minimum inhibition concentration of clarithromycin at the infection site and potentially allowed penetration of the drug inside the mucus gel. Varma et al. [75] have chemically modified guar gum (GG) as a pH-sensitive copolymer and formulated intestinal-targeting esomeprazole magnesium (ESO) nanoparticles (NPs). Polyacrylamide-grafted guar gum copolymer was synthesized by free radical polymerization, and ESO-loaded pH-sensitive NPs were prepared by nanoemulsification polymer cross-linking method. In vitro release studies showed pH-dependent drug release. The pH-sensitive NPs resisted

drug release in acidic pH and delayed the release in alkaline environment. In another study novel pH-responsive poly(methoxyethyl metacrylate-coitaconic acid) microgels were fabricated and evaluated for controlled and extended

delivery of model acid labile drug (esomeprazole). The designed microgels successfully protected the drug from acidic environment of the stomach, with potential intestinal drug delivery over an extended period of time. Thus, suggesting p(MEMA-co-IA) micro-hydrogels as good candidate of an orally administrated site-specific and controlled drug delivery system, such as proton-pump inhibitors, proteins, and peptides [76]. In similar studies p(hydroxyethyl methacrylateco-itaconic acid) microgels, poly(2-ethyl hexyl acrylate-co-IA) microgels, and poly(butyl acrylate-co-itaconic acid) microgels showed pH-responsive swelling and drug release behavior with maximum release at pH 7.4 and negligible release at pH 1.2 suggesting the potential use of these drug delivery system for oral intestinal

A novel 5-aminosalicylic acid (5-ASA)-loaded pH-sensitive poly(methoxy ethylene glycol-caprolactone-co-methacrylic acid-co-poly(ethylene glycol) dimethacrylate) microgels were prepared for treatment of ulcerative colitis. The microgels were found to be shrunk at pH 1.2 and expanded at pH 7.4. Safety evaluation of microgels was conducted by maximum tolerated dose (MTD) method. The 5-ASA/microgels were used to treat ulcerative colitis in mice, and free 5-ASA was used as positive control. It was found that 5-ASA has good efficacy for treating ulcerative colitis, and microgels entrapping 5-ASA could significantly enhance the colon targeting to improve its efficacy [80]. Xua et al. [81] fabricated novel biodegradable and pH-sensitive microgels based on poly(*ε*-caprolactone)-pluronic-poly(*ε*-caprolactone)-dimethacrylate, methyl acrylic acid, and poly(ethylene glycol)dimethacrylate cross-linked with N,N′-methylenebisacrylamide. Hydrophilic model drug (vitamin B12) was loaded to investigate in vitro release profile; the developed drug delivery system demon-

Lowman et al. [82] studied the use of poly(methacrylic-*g*-ethylene glycol) (P(MMA-*g*-EG)), a hydrogel microparticle that responds to a change in pH for the transport of orally administered insulin. This drug is a peptide labile to proteolytic degradation in the acidic stomach. Thus this pH-responsive carrier protected insulin in the acidic environment of the stomach as a result of the intermolecular interaction that prevented the hydrogel from swelling. But once the microparticles reached alkaline and neutral environments, namely, the intestine, the interaction that occurred previously was lost, and the pore size of the hydrogel increased, thus

**92**

allowing insulin release.

This chapter has attempted the compilation of the advances in the field of stimuli-responsive microgel technology and their application in controlled release drug delivery carriers. The ultimate goal for controlled drug release is to maximize therapeutic activity while minimizing the negative side effects of the drug. In this regard, versatile micro- and nanoscale delivery approaches based on smart polymers have already been established to seek the distinct advantages in drug delivery. However, the new polymers and nanocarriers definitely require extensive consideration of toxicological and immunological issues, which are often ignored during the research phase.


**5. Conclusions**

Constant leaf sprouting and development can be an indication of healthy trees in beneficial environmental circumstances. This paper investigated the feasibility of NGL detection using hyperspectral detection algorithms in UAV bitmap images. Since the bitmap images only provide RGB values, using a traditional subpixel detector CEM presents false alarm issue. In order to address this issue, three window based CEMs are proposed in this paper. First, Subset CEM is developed to split the image into different small images, according to different regions. Second, the sliding window-base CEM was proposed to extract the RGB values around the current pixel to calculate autocorrelation matrix **S**. Third, this paper further proposed adaptive window-based CEM (ASW CEM), which can change the window size automatically according to NGL around the current pixel. ASW CEM extracts and calculates autocorrelation matrix **S**, increasing the contrast between NGL and the background, so as to highlight NGLs and to suppress the background. Last but not the least, in order to reduce the effect of the quality of the desired target selected for CEM, this paper designed OSGP to generate a stable desired target during iterations. The experimental results show that our proposed approaches can effectively reduce the errors resulting from a false alarm so as to obtain more appropriate desired target and stable results for newly grown tree leaves in UAV images.

**Acknowledgments:** The authors would like to acknowledge the support provided by projects MOST 106-2221-E-224-055 and MOST 105-2119-M-415-002 funded by the Ministry of Science and Technology, Taiwan, ROC.

**Author Contributions:** S.-Y.C. conceived and designed the algorithms and wrote the paper; C.L. analyzed the data, contributed data collection, reviewed the paper and organized the revision. C.-H.T. and S.-J.C. performed the experiments.

**Conflicts of Interest:** The authors declare no conflict of interest.


5. Conclusions

Detailed knowledge of chemical properties of complex compounds could be very useful for the future investigations of new pharmacological agents. Although recent studies are trying to obtain more mechanistic information, and results provide very useful information for the future design of potential zinc- or copper-based anticancer drugs, it is evident that, up to now, this field is not investigated enough. In general, attempts to correlate the antitumour activity of zinc(II) and copper(II) compounds with coordination number and geometry could be very promising for discovery of the alternative tumour treatment.

[5] Jakupec MA, Galanski M, Keppler BK. Tumour-inhibiting platinum complexes state of the art and future perspectives. Reviews of Physiology, Biochemistry and Pharmacology.

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## Acknowledgements

The author gratefully acknowledges financial support from State University of Novi Pazar, and Ministry of Education, Science and Technological Development, Republic of Serbia (Projects No. 172011).

### Conflict of interest

No potential conflict of interest was reported by the author.

## Author details

Tanja Soldatović

Address all correspondence to<EMAIL_ADDRESS>
Department of Chemical-Technological Sciences, State University of Novi Pazar, Novi Pazar, Serbia

### References

[5] Jakupec MA, Galanski M, Keppler BK. Tumour-inhibiting platinum complexes state of the art and future perspectives. Reviews of Physiology, Biochemistry and Pharmacology. 2003;146:1-53. DOI: 10.1007/s10254-002-0001-x

5. Conclusions

Acknowledgements

jects No. 172011).

Author details

Tanja Soldatović

References

ISBN: 0-935702-57-1

Serbia

Conflict of interest

Detailed knowledge of chemical properties of complex compounds could be very useful for the future investigations of new pharmacological agents. Although recent studies are trying to obtain more mechanistic information, and results provide very useful information for the future design of potential zinc- or copper-based anticancer drugs, it is evident that, up to now, this field is not investigated enough. In general, attempts to correlate the antitumour activity of zinc(II) and copper(II) compounds with coordination number and geometry could

The author gratefully acknowledges financial support from State University of Novi Pazar, and Ministry of Education, Science and Technological Development, Republic of Serbia (Pro-

Department of Chemical-Technological Sciences, State University of Novi Pazar, Novi Pazar,

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688p. ISBN-13:<PHONE_NUMBER>776

*Edited by Takashiro Akitsu*

This book is both a review of current research and an undergraduate textbook for inorganic chemistry at university level. In university undergraduate lectures, basic concepts are mainly explained and added examples of frontier research are optional. However, in many cases, frontier research is more interesting for students than basic studies. This book is aimed at undergraduates in inorganic chemistry. Each author introduces or reviews "frontier research topics" of inorganic coordination chemistry. Additionally, "basic concepts," as found in textbooks on this subject, indicate application examples of "frontier research topics."

Published in London, UK © 2018 IntechOpen © weisschr / iStock

Basic Concepts Viewed from Frontier in Inorganic Coordination Chemistry

Basic Concepts Viewed

from Frontier in Inorganic

Coordination Chemistry

*Edited by Takashiro Akitsu*


**1. Introduction**

The main goal of laser-based gas spectroscopy research is the development of sensors with high sensitivity and selectivity, preferably maintaining a non-complex design of their setup [1–3]. According to the Beer–Lambert law, the detection ability of such sensors depends mainly on the length of the interaction path between the light beam and the measured gas molecules [4]. Hence, long optical paths implemented within the sensors setup are highly desired, especially in the case of low-concentration (typically single parts-per-million (ppm) or below—parts-per-billion (ppb) levels) gas molecules detection. Usually, long optical paths are realized by bulk-optics-based multipass cells (MPCs) that indeed fulfill this crucial requirement, however, at the expense of reduced stability of the sensor due to possible opto-mechanical drifts and optical fringes contributing to the overall noise level. Recent reports demonstrate the use of hollow-core fibers (HCFs), especially

Krzempek, K.; Hoppe, V.; Dudzik, G.; Yu, F.; Wu, D.; Liao, M.; Knight, J.; Abramski, K. Fabrication of Microchannels in a Nodeless Antiresonant Hollow-Core Fiber Using Femtosecond Laser Pulses. *Sensors* **2021**, *21*, 7591. https:// doi.org/10.3390/s21227591

**Citation:** Kozioł, P.; Jaworski, P.;

Academic Editor: Vittorio M.N. Passaro

Received: 27 October 2021 Accepted: 14 November 2021 Published: 16 November 2021

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**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

the relatively new type of such fibers, ARHCFs, as an alternative to sensors based on MPCs [5–8]. A gas-filled ARHCF can form a versatile absorption cell characterized by a small volume and can be tailored to a desired length with respect to the specific application. The filling process of the ARHCF core with the target gas mixture can be realized by either gas diffusion through both fiber ends or via specially designed gas cells located at both fiber ends, through which the gas is delivered to the hollow core using overpressure. The gas filling time can vary from several hours per meter for free gas diffusion [9,10] to a few seconds for pressure-supported methods [11–13]. A purely diffusion-based gas exchange approach is less complex; however, it significantly increases the response time of an ARHCF-based gas sensor. On the other hand, the use of overpressure filling via additional gas cells increases the sensor complexity and can negatively affect the long-term stability of the sensor. Hence, an alternative solution that will enable noninvasive, simple, and efficient gas filling of the ARHCF core is highly desired.

An alternative method of filling the ARHCF core with the target gas can be realized via side incisions that allow direct access to the fiber air core along the entire length of the fiber. This solution allows non-complex gas exchange without interfering with the optical coupling at the fiber end facets [14]. Due to the fragility of the material, noncontact processing methods are most often used. The most popular method is based on the usage of a femtosecond (fs) laser. For example, a V-shaped hole was made in an HCF [15,16] using the layer-by-layer scanning method. In [17], the researchers presented fabrication of a side hole in an HCF using an fs laser, where the process was carried out in a fluid with a matching refractive index to reduce the debris that is generated during the laser ablation process. The fabrication of microchannels with the use of femtosecond laser pulses introduces certain transmission losses, which mostly result from local damage of the fiber structure or the presence of debris generated during laser ablation.

Another noncontact method used for the production of microchannels is based on the use of a focused ion beam (FIB) as presented in [18,19] for which, due to lack of destructive factors, no losses resulting from the fabrication of the microchannel were recorded. The disadvantage of this method is the time required to process a single hole (~30 min for a single hole with a diameter of 10 μm [19]). Furthermore, because of the limited space in the FIB-based setup, it is impossible to process long (i.e., several meters) fibers in multiple places, which is required for providing optimum gas filling conditions within the long optical path provided by the fiber. For this reason, an attempt was made to find a way to improve the quality of microchannels produced using laser micromachining.

The methods of microchannel realization using an fs laser presented in the literature so far have introduced relatively high losses at the level of 0.45 dB per hole [20], and more. The lowest loss of 0.35 dB per hole was recorded for a single microchannel made in an HCF assisted by liquid [17]. These results are not satisfactory from the potential applications viewpoint since in the case where a higher number of holes is required, the total losses will effectively limit light propagation in such fiber. The most common cause of losses are local modifications of the fiber structure due to laser ablation, leading to an increased attenuation of the propagating light. An additional factor that increases losses is the debris that is formed during the process and is deposited inside the fiber. Both of these factors are the result of the non-optimized laser micromachining process used for modifying the HCF structure.

In this work, we propose a new approach based on the use of the fs laser micromachining process, enabling damage-free and efficient processing of the outer cladding of nodeless ARHCFs. To the best of our knowledge, this is the first attempt to utilize fs laser pulses to access the air core of nodeless ARHCFs via side-drilled microchannels. The developed process does not affect the cladding capillaries that define the low-loss guidance properties of this particular fiber. Such a modification in the outer structure of the ARHFC fiber, as shown in the literature [21–23], should not introduce additional transmission losses since the outer cladding has a negligible impact on the light confinement in the air core. With a properly optimized laser-micromachining process, the gap between the capillaries

can be used to directly access the hollow region of the microstructured fiber. The key element of the proposed method is the precision of laser processing and proper selection of process parameters in order to significantly reduce the formation of the debris that can accumulate in the air core of the fiber. Minimization of the debris is crucial as it significantly influences the guidance properties of ARHCFs. Here, we will compare two approaches of fabricating lateral channels in ARHCFs in terms of amount of debris, channel surface quality, and processing time. The influence of the microchannel dimensions and bending of the processed fiber will be experimentally verified.


*4.1. Exploratory Factor Analysis (EFA) and Reliability Tests*

CFA methodology recommends verifying the viability of the proposed model through EFA [36]. We, therefore, confirmed the relationships among the variables—first, to determine whether the proposed model is identified and, second, to verify the factor loadings on each of the variables. Table 4 presents the results.

**Table 4.** Consistency and internal validity, average variance extracted (AVE), and composite reliability.

**Table 4.** *Cont.*

Note: Factor loadings should be above 0.7, AVE values above 0.5, and CR scores above 0.7.

The factor loadings show consistency among the factors observed and the variables, except for item 3 (sales volume), which could be collinear with other variables and whose factor loading is below the accepted minimum of 0.7 [88]. We, therefore, excluded item 3 from the model. The other items and factors show satisfactory factor loadings, demonstrating the model's internal consistency. All values over 0.5 were accepted for average variance extracted (AVE) [36] and these values range from 0.64 to 1.00. Composite reliability (CR) values are between 0.75 and 0.99—in all cases, above 0.7, indicating construct validity [82]. Next, we present the adjusted empirical model (Figure 2).

The following values were obtained in the adjusted model: Chi-square = 363, degrees of freedom =126, standardized Chi-square = 2.88, root mean square error of approximation (RMSEA) = 0.021, Tucker–Lewis index TLI = 0.951, and incremental fit index IFI = 0.960 (these two indices should be >= 0.90). The indices for goodness of fit are incremental fit CFI = 0.960 and parsimony fit NFI = 0.940. According to theory, these values confirm the model's internal consistency, causal relationships among the variables, and good fit [82].

Next, the fact that the average of our six factors is associated with ICTS indicates that tourism business owners observed a high impact from the COVID-19 crisis. The tourism SMEs adopted remote work to reduce the impact on employment in the months of lockdown but could not sustain this measure economically over time. The measurement variable public aid to maintain payroll was crucial during the most critical months.

Item 3 (sales) in 2020 compared to 2019 measured the economic impact most precisely, showing a fall in income of 50% in over half the businesses that remained active; this calculation was obtained from the original revenue figures for 2019 and 2020, extracted from Orbis.

This item affected travel agencies in lower percentages. Many business owners had to assume the cost of reinvesting to reactivate their business to adapt to changes in technology and meet public-health requirements. Finally, the findings show that trends in both sales and payroll recovery in 2021 were factors determining whether firms were still affected by the pandemic compared to the most recent year under normal circumstances (2019). This factor strengthens indications that recovery is ongoing. Table 5 presents our evaluation of each hypothesis using the statistics obtained.

**Table 5.** Hypothesis contrast with structural model results.

#### **Table 5.** *Cont.*

Note: The regression weight obtained for the causal relationships corresponds to consolidation of the factors composing the observed endogenous variables relative to the unobserved variables.

**Figure 2.** Adjusted model.

*4.2. Business Situation (BS) When Facing the Economic Impact of the COVID-19 Crisis (ICTS)*

To test the validity of hypothesis 1 about how can the business situation of tourism SMEs in Colombia influences the level of economic impact caused by the COVID-19 crisis, we considered the weight of the regression obtained, 0.815 (Table 5), and the factor loading, 0.67. Although this factor loading is below the commonly accepted threshold of 0.7, we included it because it showed a statistically significant relationship to the criterion variable ICTS through three of the factors observed. Similarly, the t-value obtained in the hypothetical relationship is far from 0, validating the alternative hypothesis proposed, and a p-value below 0.05 permits us to reject the null hypothesis.

The economic subsector (item 1) obtained a factor loading of 0.71 (Figure 2) and a regression weight of 0.491—statistically significant values. Analysis of the percentage incomes for 2020 compared to 2019 shows that travel agencies suffered the greatest economic impact of the pandemic, with a loss of 58% income, followed by the lodging sector with 52%, and food and beverage with 40%. Tourism clubs lost 32%. We calculated these losses from the sales figures for 2019 and 2020, extracted from Orbis, classified by subsector. The percentages do not include firms that closed in 2020.

The link between number of workers (item 2) and firm size showed a factor loading of 0.77 and a regression weight of −0.676, demonstrating an inverse relationship. This finding indicates that, the larger the firm, the less severe the economic impact of the COVID-19 crisis. Sales volume (base year 2020) (item 3), did not, however, show a statistically significant factor loading. The reason may be the decrease in 2020 sales, which could exclude many companies from the SME category, as well as the incorporation into the market of new firms, for which we could not establish the degree of impact because they had no figures from previous years.

Main customers (item 4) produced a factor loading of 0.72 and a regression weight of 1.0. This result may be considered decisive for ICTs, as the statistical distribution of the variable highlights the fact that 65% of tourism SMEs sell their services primarily to consumers and families. Type of customer, thus, explains why the impact on sales was higher for these firms than for firms whose market focuses on other companies. Finally, the 11% that sell tourism services to public administrations experienced less impact from the pandemic.


*6.2.1 Thinly populated region*

The thinly populated areas of the arid region mostly cover the entire area of Baluchistan and Gilgit-Baltistan provinces. These areas comprise of hills, mountains, and barren sandy lands. Most of the land consists of rainfed areas having scared agriculture activities (**Figure 6**).


**2. Epidemiology of cardiac re-transplantation**

The number of patients undergoing ReTx has been gradually increasing over time. Between 2000 and 2005, ReTx accounted for 2.9% of all heart transplants [3]. Between January 2009 and June 2015 there were 722 patients who underwent ReTx, which constituted 3.1% of heart transplants. While this seems like a small increase over time, there has been a simultaneous shift towards more rigorous patient selection for ReTx. This shift has been a response to the uniformly poor outcomes when patients undergo ReTx for acute events like primary graft failure. In this context, the median survival of patients undergoing cardiac transplantation has increased from 8.5 years in the era of 1982–1991 to almost 12 years for patients transplanted between 2002 and 2008. Median survival is even longer in young patients, with a median survival of 12.6 years in patients undergoing initial transplant between age 18 and 39, compared to 9.1 years in patients aged 60–69. Patients under age 40 comprise 17% of the adult heart transplant population, but also represent the population most likely to require to eventually require ReTx. There is no reason to believe that there will not be an ongoing trend towards improved survival, potentially increasing the number of patients considered for ReTx.

Most of the data regarding the epidemiology of ReTx is only reflective of patients who successfully undergo ReTx. Therefore, in order to demonstrate the potential increase in candidates for ReTx, we have provided an estimate based on outcomes in current transplant recipients, shown in **Figure 1**. Currently 74% of patients are surviving at least 5 years after their initial transplant date [5]. We will assume that patients who die before this time are not candidates for ReTx given poor outcomes in patients undergoing ReTx for acute graft failure. The proportion of patients who are over age 60 at the time of initial cardiac transplant is 23.8% [5]. For the sake of a conservative estimate, we will assume that these patients are not candidates for ReTx due to advanced age. In patients who die more than 5 years after transplant, CAV accounts for 7–17% of deaths and graft dysfunction accounts for 22–40% of deaths [5]. If all patients under age 60 at initial transplant who eventually die from CAV or graft dysfunction are assessed for ReTx, then 17% of all transplant patients could potentially be ReTx eligible. There are several assumptions built into this estimate. Many patients who are potential ReTx candidates due to CAV will not be eligible due to sudden death [8], or co-morbidities that preclude ReTx. However, if even half of the patients we estimated undergo ReTx this would essentially triple the current rate of ReTx.

**3. Characteristics of cardiac re-transplant recipients**

registry data [5, 9].

Patients who undergo ReTx have characteristics distinct from those undergoing initial transplant. Some of these characteristics are related to procedures and immunosuppression required for the initial cardiac transplant. Meanwhile, other characteristics are related to surviving long enough to be considered for ReTx. However, as noted previously, this data only

**Figure 1.** Estimate of the number of patients who may be candidates for cardiac ReTx. Estimates are based on ISHLT

Cardiac Re-Transplantation: A Growing Indication with Unique Considerations

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**Figure 1.** Estimate of the number of patients who may be candidates for cardiac ReTx. Estimates are based on ISHLT registry data [5, 9].


*2.4. Characterization of RCMs and RPMs*

The RCMs and RPMs were investigated by FT-IR (MagnA-IR550, Thermo Fisher Scientific, Waltham, MA, USA) in the range 4000–400 cm−1. The analysis of the size and morphology of the RCMs and RPMs were performed using field-emission scanning electron microscopy (SEM, Supra 55 Sapphire, Carl Zeiss, Jena, Germany)). Thermogravimetric analysis of the RCMs and RPMs performed using TGA-DSC/DTA analyzer (STA 449 F5, NETZSCH-Gerätebau GmbH, Selb, Germany). The RCMs and RPMs were weighed by analytical balance with an accuracy of 0.1 mg (Practum124-1cn, Sartorius AG, Göttingen, Germany). The zeta potentials of the RCMs and RPMs were measured using a Laser Nanoparticle Size and Zeta Potential Analyzer (Zetasizer Nano, Malvern, UK). The RCM and RPM pore and specific surface area were measured at 77 k using surface area and pore size analyzer (ASAP2020, Micromeritics, Norcross, GA, USA). The mechanical properties of RCM were tested by an electronic universal testing machine (JDL-10000N, Yangzhou Tianfa test Machinery Co., Ltd., Yangzhou, China).


**1. Introduction**

Corrosion represents an important factor in the design and selection of metals and alloys for different purposes, as various corrosion mechanisms can lead to failure [1,2]. Corrosion resistance is an important criterion for selecting materials used, because the cost of their degradation due to corrosion and the associated environmental impact are quite substantial [3]. Like all metals, stainless steels can undergo chemical corrosion over time [4–6].

Corrosion manifests in different forms and depends on a multitude of physico-chemical factors (chemical composition and microstructure of the alloy, temperature, pH, chemical composition of the environment) and mechanical factors (stresses, friction) [7]. The relationship between corrosion rate and grain size has been revealed in numerous studies [8–11]. Its importance lies in the fact that this parameter can be tailored by the producers [8–11].

The austenitic steels belong to the stainless steels family and are being characterized by high Nieq and Creq [12,13]. Over time, the chemical composition, mechanical properties, resistance to corrosion, machinability and polish ability of the austenitic steels have evolved considerably, and new production processes have been developed by the steel manufacturers [14]. Each chemical element in their composition plays an important role in their properties [15], including corrosion resistance, and can be substantially modified by adding certain elements as Cu, Ti, Nb, Al, Si and Ca. Generally, the composition of austenitic stainless steels is adjusted to meet service requirements in various corrosive environments [8]. The corrosion sensitivity of austenitic steels mainly takes the form of pitting, crevice and intergranular type [16].

An important aspect which concerns the austenitic steels is the release of nickel in contact with the skin. The role of nickel in the biological response to alloys is significant with regard to toxicology and biological performance. The current trend is to eliminate nickel from alloys for medical applications. However, this needs a careful evaluation since no compromise is acceptable concerning the mechanical properties, corrosion resistance or any other possible undesirable consequences due to the substitution of nickel [7,17].

Nickel allergy is the most widespread of all contact allergies. In the European population, the prevalence of nickel allergy is of 10%–15% of adult females and 1%–3% of adult males [18–22]. Of nickel-sensitive people in the general population, 30% develop hand eczema. Teenagers and young adults tend to have a higher prevalence due to frequent body piercing.

In Europe, for objects containing nickel, intended for permanent contact with skin, Directive 94/27/EC imposed a ban if the rate of nickel release exceeds 0.5 μg/cm2·week. The subsequent Directive 2004/96/EC: "Piercing in the Human Body" specifies that the limit rate of nickel release, for these cases, is 0.2 μg/cm2·week [23–25].

The aim of this study is to evaluate the sensitivity, under the same conditions, of 17 austenitic steels of the 304, 316 and 904 series, for uniform, pitting, crevice and galvanic corrosion. Our interest was also to assess the behavior differences of the transverse surface of the samples compared to the longitudinal one.